tor amendment tagoor chemicals private limited
TRANSCRIPT
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 1
ANNEXURE – I
Details of Products as per Granted ToR and Amendment Required
S. No
Product Name
Production Capacity Ton /Month Therapeutic
category As per granted ToR
Amendment Required
1 Amitriptyline 5.00 10.00 Antidepressant
2 Atrovastatin Calcium 5.00 5.00 Hypercholesterolemia
3 Bupropion 5.00 5.00 Anti depressant
4 Clopidogrelbisulfate 5.00 5.00 Antithrombotic
5 Cyclobenzaprine HCl 5.00 5.00 Muscle relaxant
6 Cyproheptadine HCl 5.00 10.00 Anti allergic
7 Desloratadine 5.00 5.00 Antihistamine
8 Domperidone 20.00 30.00 Anti emetic
9 Domperidone maleate 2.00 2.00 Anti emetic
10 Donepezil HCl 1.00 1.00 Alzheimer’s disease
11 Ebastine 5.00 5.00 Anti allergic
12 Esomeprazole Sodium 3.00 3.00 Anti ulcerative
13 Esomeprazole Magnesium trihydrate
3.00 3.00 Anti ulcerative
14 Fexofenadine Hydrochloride 5.00 5.00 Anti histamine
15 Haloperidol 2.00 2.00 Antipsychotic
16 Itopride Hydrochloride 2.00 2.00 Antispasmodics
17 Itraconazole 10.00 15.00 Antifungal
18 Ketrolac Tromethane 2.00 2.00 Anti Inflammatory
19 Lansoprazole 10.00 10.00 Ant ulcerative
20 Loperamide Hydrochloride 10.00 10.00 Anti diarrhea agent
21 Losartan Potassium 2.00 20.00 Anti Hypertensive
22 Nebivolol HCl 2.00 2.00 Anti Hypertensive
23 Nortriptyline HCl 2.00 2.00 Anti depressant
24 Omeprazole 40.00 60.00 Ant ulcerative
25 Omeprazole Sodium 2.00 2.00 Ant ulcerative
26 Omeprazole Magnesium Dihydrate
2.00 2.00 Ant ulcerative
27 Oxatomide 1.00 1.00 Antihistamine
28
Pantoprazole Sodium Sesqui Hydrate
10.00 20.00 Ant ulcerative
29 Pimozide 2.00 2.00 Antipsychotic
30 Pregabalin 2.00 2.00 Epileptic
31 Quetiapine Hemifumarate 2.00 2.00 Antipsychotic
32 Rabeprazole Sodium 10.00 20.00 Ant ulcerative
33 Rupatadine fumarate 2.00 2.00 Antihistamine
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 2
S. No
Product Name
Production Capacity Ton /Month Therapeutic
category As per granted ToR
Amendment Required
34 Telmisartan 2.00 2.00 Anti Hypertensive
35 Terbinafine hydrochloride 10.00 15.00 Anti fungal
36 Valsartan 2.00 2.00 Anti Hypertensive
37 1-Benzy-4-piperidone 5.00 5.00 Drug Intermediate
38 1-Benzyl-4-chloropiperidine 5.00 5.00 Drug Intermediate
39 1-Benzylpiperidin-4-ol 5.00 5.00 Drug Intermediate
40 1-Methylpiperidin-4-amine 5.00 5.00 Drug Intermediate
41 4-Aminopiperidine 5.00 5.00 Drug Intermediate
42 4-Hydroxy piperidine 5.00 5.00 Drug Intermediate
43 4-Phenylpiperidine 1.00 1.00 Drug Intermediate
44 4-piperidinopiperidine 1.00 1.00 Drug Intermediate
45 N-tert-Butoxycarbonyl-4-hydroxy piperidine
5.00 5.00 Drug Intermediate
Total ( Worst Combination of any 10 Products at any given point of time)
130.00 200.00
Note:
The above Listed Products, we will manufacture either Finished Product or any
Intermediate stage of finished Product as per given quantity by not increasing the
production capacity of 200 MT/Month.
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 3
List of By-Products for ToR Amendment
S. No.
Product Name By product Quantity in
Kg /Day
1
Clopidogrel Bisulphate
Ammonium sulphate 5260 Omeprazole
Domperidone
2
Domperidone
Sodium bromide 948 Cyclobenzaprinehydrochloride
Itraconazole
3
Cyclobenzaprinehydrochloride
Magnesium Chloride 239 Cyproheptadine Hydrochloride
Desloratadine
4 Desloratadine
Potassium chloride 226 Ebastine
5 Ebastine Aluminium chloride solution (12%)
667
6 Itraconazole
Potassium bromide 117 Telmisartan
7
Pantoprazole sodium sesquihydrate Ammonium chloride 2215.57 Domperidone
8 Pantoprazole sodium sesquihydrate
Ammonium acetate 234
Acetic acid 506
Ammonium phosphate 773.50
Sodium methyl sulphate 632
9
Pantoprazole sodium sesquihydrate
Sodium acetate 1615.60 Domperidone
Rabeprazole sodium
Omeprazole
10 Omeprazole Sodium nitrite 817.50
11 Domperidone Methanol 299
12 Losartan Potassium Trityl alcohol 43.50
Total 14593.67
Note:
The By-Products will be produced according to the combination of required products
manufacturing.
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 4
ANNEXURE – II
Details of Water Consumption as per Granted ToR and Amendment Required
S.No Purpose Water consumptionIn KLD
As per granted ToR Amendment Required
1 Process 36.0 171.0
2 Washings 5.0 6.0
3 Boiler make up 58.5 71.0
4 Cooling towers make up 72.5 119.0
5 Scrubbing system 8.0 18.0
6 Domestic 5.0 6.0
7 Gardening 5.0 5.0 Total 190.0 396.0
Total Water consumption of 396 KLD, 196 KLD of water will be recovered (from
Process 81.5 KLD & Water Recycled from ZLD System 114.5 KLD). Hence, Total
fresh water requirement is 396KLD-196 KLD=200 KLD.
Source of water
As per Granted ToR: Ground Water
Amendment Required: Surface water Allotment from State Government /Ground
Water
Details of Waste Water as per Granted ToR and Amendment Required
S. No Purpose Effluent In KLD
As per granted ToR
Amendment Required
1 Process 44.0 92.0
2 Washings 5.0 6.0
3 Boiler Blow down 8.5 10.0
4 Cooling towers Blow down 10.5 15.5
5 Scrubbing system 8.0 15.0
6 Domestic 4.0 5.5
Total 80.0 144.0
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 5
ANNEXURE -III
Details of Solid & Hazardous Waste Generation and Disposal as per Granted
ToR and Amendment Required
S. No
Details Quantity
Disposal Method As per granted ToR
Amendment Required
1 Organic waste (Process Residue)
1550 Kg/Day
2133 Kg/Day
Sent to Cement Industries
2 Spent Carbon 160
Kg/Day 282
Kg/Day Sent to Cement Industries
3 Solvent Distillation Residue
1034 Kg/Day
1766 Kg/Day
Sent to Cement Industries
4 Inorganic Waste 1215
Kg/Day 796
Kg/Day Sent to TSDF
5 Spent Mixed Solvents
2303 Kg/Day
4000 Kg/Day
Sent to authorized recyclers/Cement Industries
6 ETP Sludge 500 .00 Kg/Day
500 Kg/Day
Sent to TSDF
7 MEE Salts 4387
Kg/Day 8736
Kg/Day Sent to TSDF
8
Organic Evaporative Liquid ( from MEE Stripper)
0.75KLD 1460
Kg/Day Sent to Cement Industry
9 Used Oils 500L/Annum 500L/Annum SPCB Authorized Agencies for Reprocessing/Recycling
10
Detoxified Containers
600 No’s / Month
800 No’s / Month After Detoxification sent to outside agencies.
11 Used Lead Acid Batteries
4 No’s/ Annum 4 No’s/ Annum Send back to suppliers for buyback of New Batteries
12 Ash from boiler Ash from boiler
11550 Kg/Day 17100 Kg/Day
Sent to Brick Manufacturers
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 6
ANNEXURE - IV
UTILITES AS PER GRANTED TOR
Boilers:
Existing: 6.0 TPH Coal fired/ Agro waste fired Boiler & 2,00,000 kcal/hr Thermo
pack Boiler will be continued
Proposed: 4.0 TPH Coal fired/ Agro waste fired Boiler is proposed DG Sets:
250 KVA & 500KVA
DETAILS OF UTILITIES AS PER AMENDMENT REQUIRED
Boilers:
Existing: 6.0 TPH Coal fired/ Agro waste fired Boiler will be kept as Standby
The existing 2,00,000 kcal/hr. Thermo pack Boiler will be Continued
Proposed: 12.0 TPH Coal fired/ Agro waste fired Boiler
DG Sets:
1000KVA X 2 no’s
STACK EMISSION DETAILS FOR 12 TPH COAL FIRED/ AGRO WASTE FIRED BOILER
Particulars Units 12.0 TPH Agro waste / Coal fired Boiler (Proposed)
Type of Fuel -- Agro waste /Indian Coal
Coal Consumption TPD 48
Ash Content % 35
Sulphur Content % 0.4
No. of Stacks No 1
Height of stack M 32
Diameter of Stack M 0.6
Temperature of Flue Gas
oC 220
Velocity of Flue Gas m/s 15
Particulate Matter gm/sec 1.8
Sulphur dioxide emission
gm/sec 2.67
Oxides of Nitrogen emission
gm/sec 5.13
Pollution control equipment
- Cyclone separator followed by suitable pack of Bag filters
Note : 6.0 TPH Agro waste /Coal fired boiler (Stand by )
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 7
STACK EMISSION DETAILS FOR THERMO PACK BOILER
Particulars Units 2,00,000 kcal/hr. Thermo pack
Boiler (Existing)
Thermo pack Boiler Capacity Kcal/hr. 2,00,000
Type of Fuel -- Agro waste/ Coal
Stack Temperature Before
Air preheater
oC 250
Stack Temperature After Air
preheater
oC 180
Stack Height m 9.0
Fuel Consumption per Day TPD 0.75
Diameter m 0.30
STACK EMISSION DETAILS FOR DG SETS
Capacity In KVA
Emission of SPM in mg/Nm3
Emission Of SO2 in mg/Nm3
Emission of NOx In mg/Nm3
Stack dia. in m
Flue Gas Temp. in
OC
Stack Height in m
Flue gas Velocity in m/sec.
1000 KVA (Proposed)
80 50 60 0.2 300 10 16
1000 KVA (Proposed)
80 50 60 0.2 300 10 16
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 8
ANNEXURE -VII
Details of Process Emission as per Granted ToR and Amendment Required
S. No.
Name of the Gas
Quantity In Kg/Day
As per granted ToR
Amendment Required
Treatment Method
1 Sulphur dioxide 697 2362 Scrubbed by using C.S.Lye Solution
2 Hydrogen chloride
330 439 Scrubbed by using chilled water media
3 Hydrogen Bromide
420 371 Scrubbed by using C. S. Lye solution
4 Nitrogen 14 15 Dispersed into the atmosphere
5 Carbon dioxide 630 822 Dispersed into the atmosphere
6 Hydrogen 16 30 Diffused by using Nitrogen through Flame arrestor
7 Ammonia 78 104 Scrubbed by using chilled water media
8 Oxygen 136 200 Dispersed into the atmosphere
9 Chloro Methane 17 242 Scrubbed by using C.S.Lye Solution
ToR Amendment Tagoor Chemicals Private Limited
Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 9
ANNEXURE – X
CONSOLIDATED STATEMENT- POLLUTION DETAILS ASPER TOR AMENDMEN
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 1
Form - 1
Appendix- I
(See Paragraph-6)
(I) Basic Information
S.
No. Item Details
1 Name of the Project/s
Tagoor Chemicals Private Limited (Formerly
known as Vensar Laboratories Pvt Ltd)
Expansion of Existing Bulk Drugs &
Intermediates manufacturing unit
2 S.No. in the Schedule
5(f) Synthetic organic chemicals industry (dyes
& dye intermediates; bulk drugs and
intermediates excluding drug formulations;
synthetic rubbers; basic organic chemicals,
other synthetic organic chemicals and chemical
intermediates)
3
Proposed capacity / area / length /
tonnage to be handled /command
area / lease area / number of wells
to be drilled
Bulk Drugs & Intermediates – 200 Tons/Month
(ToR Amendment)
4 New / Expansion / Modernization Expansion
5 Existing Capacity / Area etc. 10.00 TPM (As per EC vide F.No. J-11011/386/
2014-IA-II (I) Dated : 08 Jun 2017)
6 Category of Project i.e. ‘A’ or ‘B’ A
7 Does it attract the general
conditions? If yes, please specify Not Applicable
8 Does it attract the Specific
conditions? If yes, please specify. Not Applicable
9
Location Latitude 17° 9'29.20"N Longitude 81°35'29.71"E
Plot / Survey / Khasra No Sy No. 32,
Village Tupakulagudem (V)
Mandal Tallapudi (M)
District West Godavari (Dist.)
State Andhra Pradesh
10 Nearest railway station / airport
along with distance in km
Kovvuru Railway station – 22.0 KMs (SE) Rajahmundry Airport – 24.00 KMs (ESE)
11
Nearest town, city, district
headquarters along with distance in
km
Rajahmundry – 24 km (SE)
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 2
S.
No. Item Details
12
Village Panchayats, Zilla Parishad, Municipal Corporation, Local body (complete postal addresses with telephone nos. to be given)
Tupakulagudem (V) Tallapudi (M), West Godavari (Dist.), Andhra Pradesh
13 Name of the applicant P. Kasiviswanadha Raju
14 Registered Address Plot No 99 & 100, SV Cooperative Industrial Estate, IDA, Jeedimetla, Hyderabad, Telangana Sate
15
Address for Correspondence
Duplex No: 29, Lakshmi Gayatri Enclave,
Aditya Nagar, KPHB, Kukatpally, Hyderabad
Telangana Sate
Name P. Kasiviswanadha Raju
Designation (Owner/Partner/CEO) Director
Address
Duplex No: 29, Lakshmi Gayatri Enclave,
Aditya Nagar, KPHB, Kukatpally, Hyderabad
Telangana Sate
Pincode 500072
E-mail [email protected], [email protected]
Telephone no. +91-9989311222
Fax no. -
16
Details of Alternate Sites examined,
if any. Location of these sites
should be shown on a toposheet.
Not Applicable
17 Interlinked Projects Not Applicable
18
Whether separate application of
interlinked project has been
submitted.
Not Applicable
19 If yes, date of submission Not Applicable
20 If no, reason Not Applicable
21
Whether the proposal involves
approval / clearance under: if yes,
details of the same and their status
to be given
(a) The Forest (Conservation) Act,
1980?
(b) The Wildlife (Protection) Act,
1972?
Not Applicable
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 3
S.
No. Item Details
(c) The C.R.Z. Notification, 1991?
22
Whether there is any Government
Order / Policy relevant / relating to
the site
No, Government Order / Policy relevant /
relating to the site are applicable.
23 Forest Land involved (hectares) No Forest land is involved in the project
24
Whether there is any litigation
pending against the project and / or
land in which the project is
proposed to set up?
(a) Name of the Court
(b) Case No.
(c) Orders / directions of the
court, if any and its relevance with
the proposed project.
No litigations pending against the project.
(II) Activity
1. Construction, operation or decommissioning of the Project involving
actions, which will cause physical changes in the locality (topography, land
use, changes in water bodies, etc.)
S.
No.
Information / Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible)
with sources of information data
1.1
Permanent or temporary change in
land use, land cover or topography
including increase in intensity of
land use (with respect to local land
use plan).
Yes
The expansion proposal is within the
existing land. The total area of the unit
is 10.35 Acres (41885 Sq.m) and Plant
layout is Enclosed.
1.2 Clearance of existing land,
vegetation and buildings? No
No major tree felling or clearance of
buildings is envisaged.
1.3 Creation of new land uses? No None
1.4 Pre-construction investigations e.g.
bore holes, soil testing? No Not Applicable
1.5 Construction works? Yes
Construction of various blocks
Production, Stores, QC, Boiler shed,
DG set, Utility, Pollution treatment
facility, Roads, solvent storage yard,
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 4
S.
No.
Information / Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible)
with sources of information data
Green belt and others
1.6 Demolition works? No No major demolition work is envisaged
1.7
Temporary sites used for
construction works or housing of
construction works?
No
Majority of the labor will be hired from
nearby villages so no housing or
shelter facilities required for
construction workers. However existing
facilities are sufficient like drinking and
sanitation facilities for workers during
working hours.
1.8
Above ground buildings, structures
or earthworks including linear
structures, cut and fill or
excavations
No Not Applicable
1.9 Underground works including
mining or funneling? No Not Applicable
1.10 Reclamation Works? No Not Applicable
1.11 Dredging? No Not Applicable
1.12 Offshore structures? No Not Applicable
1.13 Production and manufacturing
processes? Yes
List of products, By-Products and
capacities for TOR Amendment was
Enclosed as in Additional Information
and Manufacturing Process is
Enclosed as Appendix - I
1.14 Facilities for storage of goods or
materials? Yes
Common facility for storage of raw
materials and finished products will be
provided
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 5
S.
No.
Information / Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible)
with sources of information data
1.15 Facilities for treatment or disposal
of solid waste or liquid effluents? Yes
Solid Waste: The Solid & hazardous
waste generated in plant will be
disposed as per rules. The Details of
Solid/Hazardous Waste Details as per
Amendment Required enclosed as
Annexure in Additional Information File
Liquid waste: Industrial effluent of 144
KL/ day is generated and will be
treated in ZLD System.
1.16 Facilities for long term housing of
operational workers? No
The workforce is recruited from nearby
villages. No long term housing of
operational workers
1.17 New road, rail or sea traffic during
construction or operation? No
Road traffic is likely to increase both
during construction and operation
stage for transportation of man and
material. However, existing transport
routes are adequate for the increase in
traffic. No additional transport
infrastructure is required due to the
proposed project
1.18
New road, rail, air waterborne or
other transport infrastructure
including new or altered routes and
stations, ports, airports etc?
No No, additional transport infrastructure is
required due to the present proposal.
1.19
Closure or diversion of existing
transport routes or infrastructure
leading to changes in traffic
movements?
No Not Required
1.20 New or diverted transmission lines
or pipelines? No Not Required
1.21
Impoundment, damming, culverting,
realignment or other changes to the
hydrology of watercourses or
No Not Required
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 6
S.
No.
Information / Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible)
with sources of information data
aquifers?
1.22 Stream crossings? No None
1.23 Abstraction or transfers of water
from ground or surface waters? Yes
The total water requirement is 396
KL/day for the proposed project and
Source of Water: Surface water
Allotment from River /Ground Water
1.24
Changes in water bodies or the land
surface affecting drainage or run-
off?
No
None (There will not be any changes in
water bodies or the land surface
affecting drainage or runoff)
1.25
Transport of personnel or materials
for construction, operation or
decommissioning?
No
The raw materials and products will be
transported during construction and
operation phase
1.26
Long-term dismantling or
decommissioning which could have
an impact on the environment?
No Not Applicable
1.27
Ongoing activity during
decommissioning which could have
an impact on the environment?
No Not Applicable
1.28 Influx of people to an area in either
temporarily or permanently? Yes
The Estimated employment generation
for this proposed project is about 130
Direct employees.
1.29 Introduction of alien species? No No New species are introduced.
1.30 Loss of native species or genetic
diversity? No
No Loss of native species or genetic
diversity.
1.31 Any other actions? No None envisaged
2. Use of Natural resources for construction or operation of the Project (Such
as land, water, materials or energy, especially any resources which are non-
renewable or in short supply):
S.
No.
Information /Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible)
with sources of information data
2.1 Land especially undeveloped
or agricultural land (ha) No
Total is 10.35 Acres (41885 Sq.m) of
Industrial Land
2.2 Water (expected source &
competing users) Unit : KLD Yes
The total water requirement is 396 KL/day
for the proposed project and Source of
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd) Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 7
Water: Surface water Allotment from
River /Ground Water
The Details as per Amendment Required
are enclosed in Additional Information file
2.3 Minerals (MT) No Not Applicable
2.4
Construction material – stone,
aggregates, and / soil
(expected source- MT)
No
Construction materials like stone, steel
aggregates, sand & cement will be sourced
locally.
2.5 Forests and timber (source-
MT) No No Timber will be used.
2.6
Energy including electricity
and fuels (source, competing
users) Unit : fuel (MT), energy
(MW)
Yes
Details as per Amendment Required
The power requirement for the plant is
2000 KVA.
Boilers:
The existing 6.0 TPH Coal fired/ Agro
waste fired Boiler will be kept as standby
and 2,00,000 kcal/hr Thermo pack Boiler
will be Continued.
Proposed to install 12.0 TPH Coal fired/
Agro waste fired Boiler.
DG Sets:
For emergency power supply industry is
proposing two no’s DG sets of 1000
KVA and Existing:250 KVA will be
dropped,
2.7
Any other natural resources
(use appropriate standard
units)
No None
3. Use, storage, transport, handling or production of substances or materials
which could be harmful to human health or the environment or raise concerns
about actual or perceived risks to human health.
S.
No.
Information /Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible)
with sources of information data
3.1
Use of substance or materials, which
are hazardous (as per MSIHC rules)
to human health or the environment
Yes
The number of chemicals will be used
for the production of Synthetic Drugs &
Intermediates which have been
mentioned in the list of raw materials
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 8
(flora, fauna and water supplies). given in the Additional Information as
Annexure.
3.2
Changes in occurrence of disease or
affect disease vectors (e.g. insect or
water borne diseases)
No
No such occurrence is envisaged, since
effluent generated will be treated
properly.
3.3 Affect the welfare or people e.g. by
changing living conditions? Yes
The proposed expansion will generate
direct and indirect employment
opportunities during construction as well
as operation phase for the local people
based on their qualification and work
experience.
3.4
Vulnerable groups of people who
could be affected by the project e.g.
hospital patient’s, children, the
elderly etc.,
No None
3.5 Any other causes No None
4. Production of solid wastes during construction or operation or
decommissioning (MT/ month)
S.
No.
Information / Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible
) with sources of information data
4.1 Spoil, overburden or mine wastes No
Not Applicable
4.2 Municipal waste (domestic and or
commercial wastes) Yes
Commercial waste like empty cement
bags, Iron scrap etc. will be sold to
scrap buyers after the construction
phase. Domestic waste like used
paper, label, cartoons will be disposed
to the scrap buyers. Organic waste
from canteen will be disposed as per
the local Panchayath / Municipal
disposal mechanism.
4.3
Hazardous wastes (as per
Hazardous Waste Management
Rules)
Yes
Hazardous wastes Details for ToR
Amendment are Enclosed as
Annexure in additional information
4.4 Other industrial process wastes Yes
The detailed Solid & Hazardous wastes
for ToR Amendment are Enclosed as
Annexure in additional information
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 9
S.
No.
Information / Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible
) with sources of information data
4.5 Surplus product No None
4.6 Sewage sludge or other sludge
from effluent treatment Yes ETP sludge is sent to TSDF
4.7 Construction or demolition wastes No
Minimal quantity of debris, scraps,
excavated soil used cement bags,
iron/steel scrap and cardboards waste
could be generated during additional
construction.
4.8 Redundant machinery or
equipment No None
4.9 Contaminated soils or other
materials No None
4.10 Agricultural wastes No None
4.11 Other solid wastes No None
5. Release of pollutants or any hazardous, toxic or noxious substances to air
(Kg/hr)
S.No. Information /Checklist
confirmation
Yes/
No
Details thereof (with approximate
quantities /rates, wherever possible)
with sources of information data
5.1
Emissions from
combustion of fossil fuels
from stationary or mobile
sources
Yes
Gaseous emission like SO2, NOx, CO and
particular matter shall be generated from
Boilers and DG sets which will be
maintained under prescribed limit. DG sets
will be used during only power break down.
Adequate stack height of Boilers and DG
sets provided for effective dispersion of
pollutants.
5.2 Emissions from production
processes Yes
Proper control measures will be adopted to
control emission as per prescribed
Standard
5.3
Emissions from handling
including storage and
transport
Yes
Fugitive emissions from material handling,
loading /unloading and transport of material
will be minimal due to closed loop system.
5.4 Emissions from
construction activities Yes
This will be restricted to the construction
phase and to the construction site only. It
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 10
S.No. Information /Checklist
confirmation
Yes/
No
Details thereof (with approximate
quantities /rates, wherever possible)
with sources of information data
including plant and
equipment
will be minimized by sprinkling water.
5.5
Dust or odors from
handling of materials
including construction
materials, sewage and
waste.
Yes
Dust will be generated from loading and
unloading of raw material and finished
products.
5.6 Emissions from
incineration of waste No No incinerator is proposed.
5.7
Emissions from burning of
waste in open air (e.g.
slash materials,
construction debris)
No No waste will be burnt in open air.
5.8 Emissions from any other
sources Yes
Dust Emissions from Ball Mill will be
mitigated by providing Inbuilt bag filters.
6. Generation of Noise and Vibration, and Emissions of Light and Heat:
S.No. Information /Checklist
confirmation
Yes/
No
Details thereof (with approximate
quantities /rates, wherever possible )
with sources of information data
6.1
From operation of equipment
e.g. engines, ventilation plant,
crushers
Yes
Material transport shall be source of noise
during construction, while transfer pumps,
vacuum systems are the sources of noise
during operation. The equipment in the
plant are designed for noise levels not
exceeding 90 dB (A). Proper encasement
of noise generating sources is done to
control the noise levels below 75 dB (A) at
plant boundary. Maintenance of all
equipment is carried out regularly to
reduce noise. A proper green belt is
developed which acts as a noise barrier.
6.2 From industrials or similar
processes Yes
Pumps, motors, gearboxes etc will
generate little bit of noise and will be
mitigated with regular maintenance. Apart
from all these a thick plantation of green
belt will be developed along the periphery
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 11
S.No. Information /Checklist
confirmation
Yes/
No
Details thereof (with approximate
quantities /rates, wherever possible )
with sources of information data
of the compound wall to arrest the noise
nuisance during the operation phase.
6.3 From construction or demolition Yes Temporary noise generation during
construction activities
6.4 From blasting or piling No Not Applicable
6.5 From construction or operational
traffic Yes
Noise due to movement of trucks during
construction and operation phase
6.6 From lighting or cooling systems Yes
Adequate Lighting shall be provided in
unit and also local ventilation system shall
be provided
6.7 From any other sources No Not Applicable
7. Risks of contamination of land or water from releases of pollutants into the
ground or into sewers, surface waters, groundwater, coastal waters or the sea
S.
No.
Information /Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible
) with sources of information data
7.1 From handling, storage, use or
spillage of hazardous materials Yes
Hazardous materials will be used and
stored with due safety and care at site.
All the norms under the Manufacture,
Storage and Import Of Hazardous
Chemicals (MSIHC) Rules and
amendments thereafter will be
complied.
7.2
From discharge of sewage or other
effluents to water or the land
(expected mode and place of
discharge )
No ETP will be installed and will be
designed for zero effluent discharge
7.3 By deposition of pollutants emitted
to air into the land or into water No
All possible air pollutants will be
scrubbed/ filtered properly by various
pollution control equipment before
emitting into atmosphere. The norms
will be maintained through regular
monitoring and analysis of vent gases.
7.4 From any other sources No None
7.5 Is there a risk of long term build up No None
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 12
of pollutants in the environment
from these sources?
8. Risk of accidents during construction or operation of the Project, which
could affect human or the environment
S.No. Information /Checklist
confirmation
Yes/
No
Details thereof (with approximate
quantities /rates, wherever possible
) with sources of information data
8.1
From explosions, spillages, fires
etc from storage, handling, use
or production of hazardous
substances
No
No explosions will occur during
construction. During production
operations, all inbuilt safety
precautions will be adopted and there
will not be any damage to environment
or human health.
8.2 From any other causes No None
8.3
Could the project be affected by
natural disasters causing
environmental damage (e.g.
floods, earthquakes, landslides,
cloudburst etc)?
No
As the area is plain, there are no
chances of landslides & there is no
history of cloud burst. No natural
disasters are envisaged, since site is in
an area where such occurrences do
not arise.
9. Factors which should be considered (such as consequential development)
which could lead to environmental effects or the potential for cumulative
impacts with other existing or planned activates in the locality.
S.No. Information /Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible )
with sources of information data
9.1
Lead to development of
supporting. facilities, ancillary
development or development
stimulated by the project which
could have impact on the
environment e.g.:
Supporting infrastructure
(roads, power supply, waste
Yes
The proposed project will prove
beneficiary for the localities as it
provides: Additional direct and indirect
employment
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 13
S.No. Information /Checklist
confirmation
Yes
/No
Details thereof (with approximate
quantities /rates, wherever possible )
with sources of information data
or waste-water treatment etc.)
Housing development
Extractive industries
Supply industries
Other
9.2
Lead to after use of the site,
which could have an impact on
the environment
No None
9.3 Set a precedent for later
developments No
9.4
Have cumulative effects due to
proximity to other existing or
planned projects with similar
effects)
No None envisaged
(III) Environment Sensitivity
S.
No. Areas
Yes
/No
Aerial distances (within 15 km.)
Proposed project location
boundary.
1.
Areas protected under
international conventions, national
or local legislation for their
ecological, landscape, cultural or
other related values.
No -
2.
Areas which are important or
sensitive for ecological reasons-
Wetlands, water courses or other
water bodies, coastal zone,
biospheres. Mountains, forests
Yes
Reserve Forests
Fairly dense Jungle near Gopavaram - 1.2 KMs (WNW)
Dense Mixed Jungle near Hukumpet - 4.8 KMs (NNW)
Mixed Jungle near Rajampalem - 5.1KMs (NNW)
Vinjaram R.F. -9.1 KMs(NNW)
Karakapadu RF – 9.4 KMs (NW)
Polavaram RF- 9.6 KMs (N) Water bodies
Tadipudi lift canal – 1.50 KMs (S)
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 14
S.
No. Areas
Yes
/No
Aerial distances (within 15 km.)
Proposed project location
boundary.
Tank near Bhimolu – 2.65 KMs (SW)
River Godavari– 7.8 KMs (E)
Kovada kalva - 6.25 KMs (N)
Polavaram Right Canal - 3.5 KMs (WNW)
Tank near Ramannapalem – 7.80KMs(N)
Pendrala kalva - 8.4 KMs (NW) Kovvada Kalva Reservoir – 9.62 KMs
(NW)
3.
Areas used by protected,
important or sensitive species of
flora or fauna for breeding,
nesting, foraging, resting, over
wintering, migration.
No None
4. Inland, coastal, marine or
underground waters No None
5. State, National boundaries No None
6.
Routes or facilities used by the
public for access to recreation or
other tourist, pilgrim areas
No None
7. Defense installations No None
8. Densely populated or built-up area Yes Mandal head quarter Tallapudi is 8.50 kms
9.
Areas occupied by sensitive man-
made land uses (hospitals,
schools, places of worship,
community facilities )
Yes Mandal head quarter Tallapudi is 8.50 kms
10.
Areas containing important, high
quality or scarce resources
(ground water resources, surface
resources, forestry, agriculture,
fisheries, tourism, minerals)
Yes
Reserve Forests
Fairly dense Jungle near Gopavaram - 1.2 KMs (WNW)
Dense Mixed Jungle near Hukumpet - 4.8 KMs (NNW)
Mixed Jungle near Rajampalem - 5.1KMs (NNW)
Vinjaram R.F. -9.1 KMs(NNW)
Karakapadu RF – 9.4 KMs (NW)
Polavaram RF- 9.6 KMs (N) Water bodies
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
Form-I
Prepared by Rightsource Industrial Solutions Pvt. Ltd. 15
S.
No. Areas
Yes
/No
Aerial distances (within 15 km.)
Proposed project location
boundary.
Tadipudi lift canal – 1.50 KMs (S)
Tank near Bhimolu – 2.65 KMs (SW)
River Godavari– 7.8 KMs (E)
Kovada kalva - 6.25 KMs (N)
Polavaram Right Canal - 3.5 KMs (WNW)
Tank near Ramannapalem – 7.80KMs(N)
Pendrala kalva - 8.4 KMs (NW) Kovvada Kalva Reservoir – 9.62 KMs
(NW)
11.
Areas already subjected to
pollution or environmental
damage.(those where existing
legal environmental standards are
exceeded)
No None
12.0
Areas susceptible to natural
hazard which could cause the
project to present environmental
problems (Earthquakes,
subsidence, landslides, erosion,
flooding or extreme or adverse
climatic conditions)
No
The project is located in seismic zone
II (Least Active) as per IS: 1893 (Part-
1) 2002. Therefore, possibility of
earthquake is not anticipated. So
there will be no effect of natural
hazards on the project.
ToR Amendment Tagoor Chemicals Private Limited
Appendix-I
1. 1-BENZYL-4-CHLOROPIPERIDINE
Process Description:
Stage-1:
Benzyl amine reacts with reacts with Acryclic acid methyl ester in presence of Methanol to give stage-1 product.
Stage-2:
Staeg-1 product reacts with Sodium Methoxide in presence of Hydrochloric acid and Toluene to give satge-2 product.
Stage-3:
Stage-2 product reacts with Hydrochloric acid and water in presence of Chloroform and Caustic Solution to give 1-Benzyl-4-Chloro-Piperidone.
Route of Synthesis:
Stage-1
NH2
Benzylamine
C7H9N107.15
+Acrylic acid methyl ester
O
O
C8H12O42X86.09=172.18
Methanol
3-[Benzyl-(2-methoxycarbonyl-ethyl)-amino]-propionic acid
methyl ester
OO
N
O
O
2
C15H21NO4
279.33
Manufacturing Process Page 1
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
3-[Benzyl-(2-methoxycarbonyl-ethyl)-amino]-propionic acid
methyl ester
OO
N
O
O
C15H21NO4
279.33
+ CH3ONa
Sodium methoxide
54.02
Toluene
N
OCOOCH3
1-Benzyl-4-oxo-piperidine-3-carboxylic acid methyl ester
C14H17NO3
247.29
+ HCl
36.46
+ 2 CH3OH
64.08
+ NaCl
58.44
Stage3
N
O
COOCH3
1-Benzyl-4-oxo-piperidine-3-carboxylic acid methyl ester
C14H17NO3
247.29
+ HCl
36.46
Chloroform,Caustic solution
N
Cl
1-Benzyl-4-chloropiperidone
+ CO2
44.01
C12H16ClN209.72
+ CH3OH
32.04+ H2O
18.02
+ 0.5 O216.00
Manufacturing Process Page 2
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
Stage-2
1-BENZYL-4-CHLOROPIPERIDINE
Benzylamine Acryclic acid methyl esterMethanol
Methanol RecoveryEffluent water
Toluene RecoveryEffluent water
Stage-1Sodium MethoxideHydrochloric acidToluene
Material Balance: Material Balance of 1-Benzyl-4-Chloro-Piperidone
Stage-1 Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Benzylamine 140.00 Stage-1 330.00 Acryclic acid methyl ester 224.85 Methanol Recovery 285.00 Methanol 300.00 Methanol loss 10.00 Water 400.00 Effluent water 400.00 (Water-400) 0 Organic residue 39.85 Process residue – 34.85
Distillation residue-5 (Methanol-5)
Total 1064.85 Total 1064.85
Material Balance of 1-Benzyl-4-Chloro-Piperidone Stage-2 Batch Size: 200.00 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-1 330.00 Stage-2 263.00 Sodium Methoxide 63.70 Toluene Recovery 380.00 Hydrochloric acid 43.00 Toluene loss 12.00 Toluene 400.00 Effluent water 544.54 Water 400.00 (Water-400,Sodium Chloride-
68.97,Methanol-75.57)
Organic residue 37.16 Process residue-29.16
Distillation residue-8 (Toluene-8)
Total 1236.70 Total 1236.70
Manufacturing Process Page 3
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of 1-Benzyl-4-Chloro-Piperidone Stage-3 Batch Size: 200.00 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-2 263.00 1-Benzyl-4-Chloro-Piperidone 200.00 Hydrochloric acid 38.65 Chloroform Recovery 475.00 Chloroform 500.00 Chloroform Loss 25.00 Caustic solution 50.00 Effluent water 383.93 Water 300.00 (Water-300,Water from Caustic
solution 50,Generated Methanol-33.93)
Process emission 63.38 (carbondioxide-46.55, oxygen-
16.83)
Organic residue 4.34 Process residue -4.34 Total 1151.65 Total 1151.65
2. 1-BENZYL-4-PIPERIDONE Process Description: Stage-1: Benzyl amine reacts with reacts with Acryclic acid methyl ester in presence of
Methanol to give stage-1 product.
Stage-2: Staeg-1 product reacts with Sodium Methoxide in presence of Hydrochloric acid and
Toluene to give satge-2 product.
Stage-3: Stage-2 product undergoes Hydrolysis with Sodium Hydroxide and Hydrochloric acid
in presence of Chloroform to give 1-Benzyl-4-Piperidone.
Route of Synthesis: Satge-1
NH2
Benzylamine
C7H9N107.15
+
Acrylic acid methyl ester
O
O
C8H12O42X86.09=172.18
Methanol
3-[Benzyl-(2-methoxycarbonyl-ethyl)-amino]-propionic acid
methyl ester
O
O
N
O
O
2
C15H21NO4
279.33
Manufacturing Process Page 4
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
3-[Benzyl-(2-methoxycarbonyl-ethyl)-amino]-propionic acid
methyl ester
O
O
N
O
O
C15H21NO4
279.33
+ CH3ONa
Sodium methoxide
54.02
Toluene
N
O
COOCH3
1-Benzyl-4-oxo-piperidine-3-carboxylic acid methyl ester
C14H17NO3
247.29
+ HCl
36.46
+ 2 CH3OH
64.08
+ NaCl
58.44
Stage-3
N
O
COOCH3
1-Benzyl-4-oxo-piperidine-3-carboxylic acid methyl ester
C14H17NO3
247.29
+ HCl
36.46
Chloroform,Caustic solution
N
O
1-Benzyl-4-piperidone
+ NaOH
40.00C12H15NO
189.25
+ CH3OH32.04
+ + CO2
44.01NaCl
58.44
Manufacturing Process Page 5
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
Stage-2
1-BENZYL-4-PIPERIDONE
Benzylamine Acryclic acid methyl esterMethanol
Methanol RecoveryEffluent water
Toluene RecoveryEffluent water
Stage-1Sodium MethoxideHydrochloric acidToluene
Stage-2 Chloroform RecoveryEffluent water
Stage-2Hydrochloric acidChloroform Caustic solution Sodium Hydroxide
Material Balance:
Material Balance of 1-Benzyl-4- Piperidone Stage-1
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Benzylamine 147.00 Stage-1 350.00 Acryclic acid methyl ester 236.00 Methanol Recovery 285.00 Methanol 300.00 Methanol loss 10.00 Water 400.00 Effluent water 400.00 (Water-400) Organic residue 38.00 Process residue – 33
Distillation residue-5 (Methanol-5)
Total 1083.00 Total 1083.00
Manufacturing Process Page 6
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of 1-Benzyl-4- Piperidone Stage-2
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 350.00 Stage-2 285.00 Sodium Methoxide 67.55 Toluene Recovery 380.00 Hydrochloric acid 45.50 Toluene loss 12.00 Toluene 400.00 Effluent water 553.30 Water 400.00 (Water-400,Sodium Chloride-
73.15,Methanol-80.15)
Organic residue 32.75 Process residue-24.15
Distillation residue-8 (Toluene-8)
Total 1263.05 Total 1263.05
Material Balance of 1-Benzyl-4- Piperidone Stage-3
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 285.00 1-Benzyl-4- Piperidone 200.00 Hydrochloric acid 42.00 Chloroform Recovery 475.00 Chloroform 500.00 Chloroform Loss 25.00 Caustic solution 50.00 Effluent water 454.02 Sodium Hydroxide 45.88 (Water-300,Water from Caustic
solution 50,Generated Methanol-36.76,Sodium Chloride-67.26)
Water 300.00 Process emission 50.45 (carbondioxide-50.45) Organic residue 18.41 Process residue -18.41 Total 1222.88 Total 1222.88
Manufacturing Process Page 7
ToR Amendment Tagoor Chemicals Private Limited
3. 1-BENZYL-PIPERIDIN-4-OL
Process Description:
Stage-1:
N-Benzyl-4-Piperidone undergoes Hydrogenation with Hydrogen in presence of Palladium Carbon and Methanol to give 1-Benzyl-piperidin-4-ol
Route of Synthesis:
Stage-1
N
O
N-Benzyl-4-piperidone
C12H15NO189.25
+ H2
2.02
Methanol,Pd/C
N
OH
C12H17NO
191.27
1-Benzyl-piperidin-4-ol
Flowchart:
Stage-1
1-BENZYL-PIPERIDIN-4-OL
N-Benzyl-4-PiperidoneHydrogen Methanol
Methanol RecoveryEffluent water
Manufacturing Process Page 8
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of 1-Benzyl-Piperidin-4-ol .Stage-1
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg N-Benzyl-4-Piperidone 209.00 1-Benzyl-piperidin-4-ol 200.00 Hydrogen 2.20 Methanol Recovery 285.00 Methanol 300.00 Methanol loss 10.00 Water 400.00 Effluent water 400.00 (Water-400) Organic residue 16.20 Process residue – 11.20
Distillation residue-5 (Methanol-5)
Total 911.20 Total 911.20
4. 1-METHYLPIPERIDIN-4-AMINE
Process Description:
Stage-1:
1-methylpiperidin-4-one undergoes amination with Ammonia in presence of Methanol to give 1-Methylpiperidin-4-Amine
Route of Synthesis
Stage-1:
1-methylpiperidin-4-one
N
O
CH3
C6H11NO113.16
Methanol,Methanolic ammonia
Raney Nickel,H2 gas
1-methylpiperidin-4-amine
N
NH2
CH3
C6H14N2
114.19
NH3
17.03
+ 0.5 O2
16.00
+
Manufacturing Process Page 9
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
1-METHYLPIPERIDIN-4-AMINE
1-methylpiperidin-4-oneAmmoniaMethanol Raney nickel Hydrogen gasMethanolic ammonia
Methanol RecoveryEffluent water
Material balance:
Material Balance of 1-Methylpiperidin-4-Amine Stage-1
Batch Size: 200.00 Kg Name of the input Quantity in
Kg Name of the out put Quantity
in Kg 1-methylpiperidin-4-one 209.00 1-Methylpiperidin-4-Amine 200.00 Ammonia 31.35 Methanol Recovery 385.00 Methanol 400.00 Methanol Loss 10.00 Raney nickel 10.00 Effluent water 407.00 Hydrogen gas 2.00 (Water-400,Methanolic ammonia-
5,Hydrogen-2) 0
Methanolic ammonia 5.00 Raney nickel recovery 10.00 Water 400.00 Process emission 29.46 (oxygen-29.46) 0 Organic residue 15.89 Process residue -10.89
Distillation residue-5 (Methanol-5)
Total 1057.35 Total 1057.35
Manufacturing Process Page 10
ToR Amendment Tagoor Chemicals Private Limited
5. 4-AMINO PIPERIDINE
Process Description:
Stage-1:
N-carbethoxy-4-amino-Piperidine reacts with Sodium hydroxide and Hydrochloric acid in presence of water and Chloroform to give 4-Amino-Piperidine.
Route of Synthesis:
Stage-1
N
NH2
COOC2H5
N-Carbethoxy-4-amino piperidine
C8H16N2O2
172.22
+ NaOH
40.00
+ HCl
36.46
Water,Chloroform N
H
NH2
4-Amino piperidine
C5H12N2
100.16
+ C2H5OH
Ethanol46.07
+ NaCl58.44
+ CO2
44.01
Flowchart:
Stage-1
4-AMINO PIPERIDINE
N-Carbethoxy-4-amino piperidineSodium HydroxideHydrochloric acidChloroform
ChloroformRecoveryEffluent water
Manufacturing Process Page 11
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of 4-Amino-Piperidine. Stage-1
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg
N-Carbethoxy-4-amino piperidine 367.00 4-Amino-Piperidine 200.00
Sodium Hydroxide 85.15 Chloroform Recovery 285.00 Hydrochloric acid 77.45 Chloroform loss 15.00 Chloroform 300.00 Effluent water 622.39 Water 400.00 (Water-400, sodium chloride-
124.41,Ethanol-97.98) 0
Process emission 93.58 (Carbon dioxide-93.58) 0 Organic residue 13.63 Process residue – 13.63 Total 1229.60 Total 1229.60
6. 4-HYDROXY PIPERIDINE
Process Description:
Stage-1:
N-Methyl-4-Piperidone reacts with Ethylchloroformate in presence of Toluene to give Satge-1 product.
Stage-2:
Stage-1 product undergoes Hydrogenation with Hydrogen gas in presence of Toluene and Raney nickel to give Stage-2 product. Stage-3: Stage-2 product undergoes hydrolysis with sodium hydroxide in presence of Toluene to give 4-Hydroxy piperidine.
Manufacturing Process Page 12
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1:
N
O
CH3
N-Methyl-4-Piperidone
C6H11NO
113.16
N
O
OO
CH3
ClO
OCH3
Ethylchloroformate
+
C3H5ClO2
108.52
4-Oxo-piperidine-1-carboxylic acid ethyl ester
C8H13NO3
171.19
+ CH3Cl
50.49
Chloromethane
Stage-2:
N
O
OO
CH3
4-Oxo-piperidine-1-carboxylic acid ethyl ester
C8H13NO3
171.19
N
OH
OO
CH3
4-Hydroxy-piperidine-1-carboxylic acid ethyl ester
C8H15NO3
173.21
+ H2
2.0
Manufacturing Process Page 13
ToR Amendment Tagoor Chemicals Private Limited
Stage-3:
N
OH
OO
CH3
4-Hydroxy-piperidine-1-carboxylic
acid ethyl esterC8H15NO3
173.21
NH
OH
+ NaOH
80.00
C5H11NO
101.15
4-Hydroxy Piperidine
2+ C2H5OH
46.07
+ Na2CO3
105.99
Flowchart:
Stage-1
4-HYDROXY PIPERIDINE
N-Methyl-4-PiperidoneEthylchloroformateTolueneAcetic acid C.S.Lye
Toluene RecoveryEffluent water
Stage-2Stage-1HydrogenRaney NickelToluene
Toluene RecoveryEffluent water
Stage-3Stage-2Sodium hydroxideToluene
Toluene RecoveryEffluent water
Manufacturing Process Page 14
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material balance of 4-Hydroxy Piperidine Stage-1
Batch Size:100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg N-Methyl-4-Piperidone 130.00 Stage-1 188.00 Ethylchloroformate 124.55 Toluene Recovery 375.00 Toluene 400.00 Toluene Loss 15.00 Acetic acid 3.00 Effluent Water 359.09 C.S.Lye 2.00 (Water-350, Toluene-5,
Sodium acetate-4.09)
Water 350.00 Process Emission 57.98 (Chloromethane-57.98) Organic Residue 14.48 Process residue-9.48
Distillation residue-5 (Toluene-5)
Total 1009.55 Total 1009.55
Material balance of 4-Hydroxy Piperidine Stage-2
Batch Size:100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 188.00 Stage-2 180.00 Hydrogen 2.05 Toluene Recovery 332.00 Raney Nickel 10.00 Toluene Loss 15.00 Toluene 350.00 Raney Nickel reuse 10.00 Water 300.00 Effluent Water 302.00 (Water-300,Toluene-2) Organic Residue 11.05 Process residue-10.05
Distillation residue-1 (Toluene-1)
Total 850.05 Total 850.05
Manufacturing Process Page 15
ToR Amendment Tagoor Chemicals Private Limited
Material balance of 4-Hydroxy Piperidine Stage-3
Batch Size:100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 180.00 4-Hydroxy Piperidine 100.00 Sodium hydroxide 83.20 Toluene Recovery 285.00 Toluene 300.00 Toluene Loss 10.00 Water 300.00 Effluent Water 459.68 (Water-300,Ethanol-
47.7,Sodium carbonate-109.98,Toluene-2)
Organic Residue 8.52 Process residue-5.52
Distillation residue-3 (Toluene-3)
Total 863.20 Total 863.20
7. 4-PHENYLPIPERIDINE
Process Description:
Stage-1:
4-Phenyl-piperidin-4-ol reacts with Sulphuric acid and Sodium Hydroxide in presence of Toluene to give 4-Phenyl Piperidine
Manufacturing Process Page 16
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
NH
OH
4-Phenyl-piperidin-4-olC11H15NO
177.24
+ H2SO4
98.08
+ 2 NaOH
80.00
Toluene NH
4-Phenyl-piperidineC11H15N
161.24
+ Na2SO4
Sodium sulphate
142.04
+ 2 H2O
36.03
+ 0.5 O2
16.00
Flowchart:
Stage-1
4-PHENYLPIPERIDINE
4-Phenyl-piperidin-4-olSodium HydroxideSulphuric acidToluene
Toluene RecoveryEffluent water
Manufacturing Process Page 17
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of 4-Phenyl Piperidine. Stage-1
Batch Size: 100.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg
4-Phenyl-piperidin-4-ol 118.00 4-Phenyl Piperidine 100.00
Sodium Hydroxide 53.25 Toluene Recovery 285.00 Sulphuric acid 65.25 Toluene loss 10.00 Toluene 300.00 Effluent water 521.47 Water 400.00 (Water-400, sodium Sulphate-
94.52,Generated water-23.95,Toluene-3)
0
Process emission 10.62 (Oxygen-10.62) 0 Organic residue 9.41 Process residue – 7.41
Distillation residue-2 (Toluene-2)
Total 936.50 Total 936.50
8. 4-PIPERIDINOPIPERIDINE
Process Description:
Stage-1:
4-Oxo-piperidine-1-carboxylic acid ethyl ester reacts with Piperidine in presence of Hydrogen,Pd/c and Methanol to give Stage-1 product.
Staeg-2:
Staeg-1 Product undergoes Hydrolysis with Potassium Hydroxide and Hydrochloric acid in presence of IPA to give 4-Piperidinopiperidine
Manufacturing Process Page 18
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
N
O
COOC2H5
4-Oxo-piperidine-1-carboxylic acid ethyl ester
C8H13NO3
171.19
+ NH
PiperidineC5H11N
85.15
+ H2
2.02
Pd/C,Methanol,
3-4Kg pressureN
N
COOC2H5
[1,4']Bipiperidinyl-1'-carboxylic acid ethyl ester
C13H24N2O2
240.34
+ H2O
18.02
Stage-2
N
N
COOC2H5
[1,4']Bipiperidinyl-1'-carboxylic acid ethyl ester
C13H24N2O2
240.34
+ KOH
Potassium hydroxide
56.11
+ HCl
36.46
IPA NH
N
4-Piperidinopiperidine
C10H20N2
168.28
+ C2H5OH
46.07Ethanol
+ KCl
74.55
+ CO2
44.01
Manufacturing Process Page 19
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
4-PIPERIDINOPIPERIDINE
4-Oxo-piperidine-1-carboxylic acid ethyl esterPiperidine Methanol Palladium carbonHydrogen
Methanol RecoveryEffluent water
Stage-1Potassium HydroxideHydrochloric acidIPA
IPA recoveryEffluent waterStage-2
Material Balance:
Material balance of 4-Piperidinopiperidine Stage-1
Batch Size:100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 4-Oxo-piperidine-1-carboxylic acid ethyl ester
116.00 Stage-1 152.00
Piperidine 57.65 Methanol Recovery 385.00 Methanol 400.00 Methanol Loss 10.00 Palladium carbon 1.00 Effluent Water 362.18 Hydrogen 1.25 (Water-350, Generated
water-12.18) 0
Water 350.00 Organic Residue 16.72 Process residue-11.72
Distillation residue-5 (Methanol-5)
Total 925.90 Total 925.90
Manufacturing Process Page 20
ToR Amendment Tagoor Chemicals Private Limited
Material balance of 4-Piperidinopiperidine Stage-2
Batch Size:100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 152.00 4-Piperidinopiperidine 100.00 Potassium Hydroxide 35.42 IPA Recovery 385.00 Hydrochloric acid 22.95 IPA Loss 15.00 IPA 400.00 Effluent Water 426.15 Water 350.00 (Water-350, Ethanol-
29.03,Potassium chloride-47.12)
0
Process Emission 27.82 (Carbondioxide-27.82) 0 Organic Residue 6.40 Process residue-6.40 Total 960.37 Total 960.37
AMITRIPTYLINE HYDROCHLORIDE
Process Description:
Stage-1: Step-A: 1-bromo-3-chloropropane (BCP) reacts with Dimethylamine (DMA) the presence of
Toluene, water, C.S Lye, HCl, Potassium hydroxide and Sodium Sulphate to give
Step-A product.
Step-B: Step-A product reacts with Hydrochloric acid to give stage-1 Product.
Stage 2:
Step-A:
Isobenzofuran-1,3-dione reacts with Phenyl acetic acid in presence of Sodium
acetate and Potassium Hydroxide Solution to give Step-A Product.
Step-B:
Step-A Product undergoes Hydrogenation in presence of Raney nickel and Toluene
to give step-b product.
Manufacturing Process Page 21
ToR Amendment Tagoor Chemicals Private Limited
Step-C:
Step-B product undergoes dehydration with Phosphorous Pent oxide and
Phosphoric acid in presence of O-xylene to give Stage-2 product.
Stage-3:
Stage-2 product reacts with Stage-1 product in presence of Magnesium, Ammonium
Chloride, THF and Methanol to give stage-3 product.
Stage-4:
Stage-3 product undergoes Salt formation/Dehydration with Hydrochloric acid in
presence of Toluene, Carbon and Acetone to give Amitriptyline Hydrochloride
Route of Synthesis
Stage-1: Step-A
HNCH3CH3
N-methyl methanamineBr Cl
1-bromo-3-chloropropane
Cl N
3-chloro-N,N-dimethylpropan-1-amine
Toluene, water, HCL
KOH, Sodium sulphate
NaBr
Sodium bromide
NaOH
sodium Hydroxide
H2O
+
C2H7N45.08
C3H6BrCl157.44
40.00
C5H12ClN121.61
102.918.0
Step-B:
Cl N
CH3
CH3
3-chloro-N,N-dimethylpropan-1-amine Hydrochloride
C5H13Cl2N
+ HCl
36.46
. HCl
158.07
Cl N
CH3
CH3
3-chloro-N,N-dimethylpropan-1-amine
C5H12ClN
121.61
Manufacturing Process Page 22
ToR Amendment Tagoor Chemicals Private Limited
Stage-2:
Step-A:
O
O
O
Isobenzofuran-1,3-dioneC8H4O3
148.12
+
O
OH
Phenyl-acetic acidC8H8O2
136.15
CH3COONaO
O
3-Benzylidene-3H-isobenzofuran-1-one
C15H10O2
222.24
+ CO2
44.0
+ H2O
18.02
Step-B:
Raney NiToluene
O
O
3-Benzylidene-3H-isobenzofuran-1-one
C15H10O2
222.24
O
OH
2-Phenethyl-benzoic acid
C15H14O2
226.27
+ 2 H2
4.00
Step-C:
XyleneO
OH
2-Phenethyl-benzoic acidC15H14O2
226.27
O
DibenzosuberoneC15H12O
208.26
+ H2O
18.0
P2O5 ,H3PO4,C.S.LYE
Manufacturing Process Page 23
ToR Amendment Tagoor Chemicals Private Limited
Stage-3:
O
Dibenzosuberone
C15H12O
208.26
+Cl N
CH3
CH3
3-chloro-N,N-dimethylpropan-1-amine
C5H12ClN
121.61
+ Mg + NH4Cl
N
OH
24.31 53.49
5-(3-Dimethylamino-propyl)-10,11-dihydro-5H-dibenzo[a,d]
cyclohepten-5-olC20H25NO295.42
+ MgCl2 + NH3
95.21 17.03
THF/Methanol
Stage-4:
N
OH
5-(3-Dimethylamino-propyl)-10,11-dihydro-5H-dibenzo[a,d]
cyclohepten-5-olC20H25NO
295.42
+ HCl
36.46
N
HCl
Amitriptyline HydrochlorideC20H24ClN
313.86
Acetone
Carbon+ H2O
18.0
Manufacturing Process Page 24
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart
Stage-1
Stage-2
1-Bromo-3-Chloro propaneDi methyl amineTolueneSodium HydroxideSodium sulfate.Hydrochloric Acid
Toluene recoveryEffluent water
Isobenzofuran-1,3-dionePhenyl-acetic acidPotassium hydroxideSodium acetateToluene Raney NickelHydrogenXylene CS Lye Flakes (10%)
Toluene RecoveryXylene RecoveryEffluent water
AMITRIPTYLINE HYDROCHLORIDE
Stage-3
Stage-4Toluene recoveryAcetone recoveryEffluent water
Toluene RecoveryMethanol RecoveryEffluent water
Stage-23-Chloro-N,N-dimethylpropan-1-amineAmmonium ChlorideMagnesiumTetra hydro furanTolueneMethanol
Stage-3Hydrochloric Acid TolueneAcetoneActivated Carbon
Manufacturing Process Page 25
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of Amitriptyline Hydrochloride Stage-1
BatchSize:500 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 1-Bromo-3-Chloro propane 225.00 Stage-1 205.00 Di methyl amine 65.00 Toluene Recovery 475.00 Toluene 500.00 Toluene Loss 10.00 Sodium Hydroxide 57.00 Effluent Water 580.83 Sodium sulfate. 20.00 (water-400, Generated water-
25.83, Sodium Bromide-147, Toluene-8)
Hydrochloric Acid 50.00 Inorganic solid waste 20.00 Water 400.00 (Sodium sulfate) Organic residue 26.17 Process residue-21.17
Distillation residue-5 (Toluene-5)
Total 1317.00 Total 1317.00
Material Balance of Amitriptyline Hydrochloride Stage-2
BatchSize:500 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Isobenzofuran-1,3-dione 290.00 Stage-2 350.00 Phenyl-acetic acid 267.00 Xylene Recovery 385.00 Potassium hydroxide 50.00 Xylene Loss 10.00 Sodium acetate 10.00 Toluene Recovery 1140.00 Toluene 1200.00 Toluene Loss 40.00 Raney Nickel 20.00 Effluent Water 807.10 Hydrogen
7.50
(water-500, Generated water-67.10, Sodium acetate-10, Potassium Hydroxide-50, Phosphoric acid-50, Phosphorous Pent oxide-30, Water from CS Lye-90,Toluene-10)
Phosphorous Pent oxide 30.00 Process emission 86.14 Phosphoric acid 50.00 (carbondioxide-86.14) Xylene 400.00 Organic residue 106.26 CS Lye Flakes (10%)
100.00 Process residue-91.26 Distillation residue-15 (Xylene-5,Toluene-10)
Water 500.00 Total 2924.50 Total 2924.50
Manufacturing Process Page 26
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Amitriptyline Hydrochloride Stage-3
BatchSize 500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 350.00 Stage-3 480.00 3-Chloro-N,N-dimethylpropan-1-amine
205.00 Tetra hydro furan Recovery 238.00
Ammonium Chloride 90.00 Tetra hydro furan Loss 12.00 Magnesium 41.00 Toluene Recovery 95.00 Tetra hydro furan 250.00 Toluene Loss 3.00 Toluene 100.00 Methanol Recovery 190.00 Methanol 200.00 Methanol Loss 5.00 Water 500.00 Effluent Water 661.00 Water-500, Magnesium
Chloride-160,Toluene-1)
Process Emission 28.62 (Ammonia-28.62) Organic Residue 23.38 Process residue-17.38
Distillation residue-6 (Toluene-1,Methanol-5)
Total 1736.00 Total 1736.00
Material Balance of Amitriptyline Hydrochloride Stage-4
BatchSize 500 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 480.00 Amitriptyline Hydrochloride 500.00 Hydrochloric Acid 62.00 Toluene Recovery 570.00 Toluene 600.00 Toluene Loss 12.00 Acetone 250.00 Acetone Recovery 237.00 Activated Carbon 20.00 Acetone Loss 12.00 Water 400.00 Spent Carbon 20.00 Effluent water 433.28 (water-400,Generated water-
29.28,Toluene-4)
Organic Residue 27.72 Process residue-22.72,
Distillation residue-5 (Toluene-4,Acetone-1)
Total 1812.00 Total 1812.00
Manufacturing Process Page 27
ToR Amendment Tagoor Chemicals Private Limited
ATROVASTAIN CALCIUM
Process Description:
Stage-1
tert-Butyl-2-[(4R,6S)-6-(cyano methyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate
undergoes reduction with Hydrogen on Palladium Carbon in presence of Methanol to
give Stage-1 Product.
Stage-2
Aniline undergoes condensation with Dimethyl Carbonate and 2-Methyl-2-butanone
in presence of Methanol to give stage-2 product.
Stage-3
Stage-2 product reacts with Benzaldehyde in presence of potassium Carbonate,
Acetone and Toluene media to give stage-3 product.
Stage-4
Stage-3 Product reacts with stage-1 product and Fluorobenzaldehyde in presence of
Para Toulene Sulfonic acid, Isopropyl Alcohol and Toluene to give stage-4 product.
Stage-5
Stage- 4 product undergoes hydrolysis in presence of Sulfuric acid and Methanol to
give Stage-5 Product.
Stage-6
Stage-5 product undergoes salt formation with Calcium Acetate in presence of
Isopropyl Alcohol to give Atorvastatin Calcium.
Manufacturing Process Page 28
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
CNO
CH3CH3
CH3
OOO
CH3H3C
+ 2 H2NH2 O
CH3CH3
CH3
OOO
CH3H3C
tert-Butyl-2[(4R,6S)-6-(cyano methyl)-2,2-dimethyl-1,3-dioxan-4yl] acetate
269.34
tert-Butyl-2[(4R,6S)-6-(amino ethyl)-2,2-dimethyl-1,3-dioxan-4yl] acetate
273.37
C14H23NO4
4.0
C14H27NO4
Methanol
Stage-2
NH2CH3H3C
H3C O
+ ++
Aniline
93.13
Dimethyl carbonate
90.08
2-Methyl-2-butanone
86.13
2 CH3OH
205.25
64.08
C6H7N C3H6O3
O
O
O
C5H10OC12H15NO2
4-Methyl-3-oxo-N-phenylpentanamide
CH3
O
HN
OCH3
Methanol
Manufacturing Process Page 29
ToR Amendment Tagoor Chemicals Private Limited
Stage-3
205.25
C12H15NO2
4-Methyl-3-oxo-N-phenylpentanamide
CH3
O
HN
O
CH3 H
O
Benzaldehyde
106.12
C7H6O
+ + K2CO3
138.20
C19H19NO2
293.36
+ 2KCl
149.10
+ CO2
44.01
2-Benzylidene-4-methyl-3-oxo-pentanoic acid phenylamide
CH3
O
NH
OH3C
+ 2 HCl
72.92
+ 2 H2O
36.04
Acetone, Toluene
Stage-4
C19H19NO2
293.36
+
2-Benzylidene-4-methyl-3-oxo-
pentanoic acid phenylamide
CH3
O
NH
OH3C
H
O
F
+NH2 O
CH3CH3CH3
OOO
CH3H3C
tert-Butyl-2[(4R,6S)-6-(amino ethyl)-2,2-dimethyl-1,3-dioxan-4yl] acetate
273.37
Fluorobenzaldehyde
124.03C14H27NO4
C7H5FO
2 H2O+
Atorvastatin Ester
654.81
NNH
O H3CCH3
F
O OH3C CH3
O
O CCH3
CH3CH3
C40H47FN2O5
36.04
IPA
Toluene
Manufacturing Process Page 30
ToR Amendment Tagoor Chemicals Private Limited
Stage-5
+
Atorvastatin Ester
654.81
NNH
O H3CCH3
F
O OH3C CH3
O
O CCH3
CH3CH3
C40H47FN2O5
2 H2O
CH3H3C
O
+ + C CH3
CH3
CH3
OH
Atorvastain
558.64
Acetone
58.08
tert-Butanol
74.12
36.0
NNH
O H3CCH3
F
OH OH O
OH
C33H35FN2O5
C3H6O C4H10O
Methanol
Stage-6
+
Atorvastain
1117.28
NNH
O H3CCH3
F
OH OH O
OH
C33H35FN2O5
CH3COOCa
Calcium Acetate
99.12
NNH
O H3CCH3
F
OH OH O
OH
Atorvastatin calcium
60.04
CH3COOH
C66H68CaF2N4O10
2
2
Ca2+
+
1155.36
Iso Propyl alcohol
Manufacturing Process Page 31
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart: Tert-Butyl-2-[(4R,6S)-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-yl]AcetatePalladium CarbonHydrogenMethanol
Stage-1Methanol RecoveryPalladoum carbon recovery
Stage-2Methanol RecoveryEffluent water
AnilineDimethyl Carbonate2-Methyl-2-ButanoneSulfuric AcidMethanol
Stage-3
Acetone RecoveryToluene RecoveryEffluent water
Stage-2BenzaldehydePotassium CarbonateHydrochloric acidAcetoneToluene
Stage-4Toluene RecoveryIsopropyl alcohol RecoveryEffluent water
Stage-3Stage-1FluorobenzaldehydeToluenePara Toluene Sulfonic AcidIsopropyl Alcohol
Stage-5Methanol RecoveryEffluent water
Stage-4Sulfuric AcidMethanol
Stage-6IPA RecoveryAcetic acid recovery
Calcium AcetateIsopropyl AlcoholActivated Carbon
ATORVASTATIN CALCIUM
Manufacturing Process Page 32
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of Atorvastatin Calcium Stage-1
Batch Size:200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Tert-Butyl-2-[(4R,6S)-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-yl]Acetate
131.00 Stage-1 122.00
Palladium Carbon 1.00 Methanol Recovery 380.00 Hydrogen 1.85 Methanol Loss 15.00 Methanol 400.00 Palladium Carbon 1.00 Organic residue- 15.85 Process residue-10.85
Distillation residue-5 (Methanol-5)
Total 533.85 Total 533.85
Material Balance of Atorvastatin Calcium Stage-2
Batch Size:200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Aniline 50.00 Stage-2 100.00 Dimethyl Carbonate 48.35 Methanol Recovery + generated
Methanol 177.40
2-Methyl-2-Butanone 46.00 Methanol Loss 4.00 Sulfuric Acid 0.80 Effluent Water 300.80 Methanol 150.00 (Water-300,Sulfuric acid-0.8) Water 300.00 Organic Residue 12.95 Process residue-9.95
Distillation residue-3 (Methanol-3)
Total 595.15 Total 595.15
Manufacturing Process Page 33
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Atorvastatin Calcium Stage-3
Batch Size:200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 100.00 Stage-3 131.00 Benzaldehyde 51.50 Acetone Recovery 190.00 Potassium Carbonate 67.00 Acetone Loss 5.00 Hydrochloric acid 35.50 Toluene Recovery 285.00 Acetone 200.00 Toluene Loss 8.00 Toluene 300.00 Effluent Water 494.10 Water 400.00 (Water-400,Generated water-
17.50,Potassium Chloride-72.60, Toluene-4)
Process Emission 21.40 (Carbon dioxide- 21.40) Organic residue 19.50 Process residue-11.50
Distillation residue-8 (Toluene-3, Acetone-5)
Total 1154.00 Total 1154.00
Material Balance of Atorvastatin Calcium Stage-4
Batch Size:200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 131.00 Stage-4 268.00 Stage-1 122.00 Isopropyl Alcohol Recovery 285.00 Fluorobenzaldehyde 55.00 Isopropyl Alcohol Loss 10.00 Toluene 500.00 Toluene Recovery 475.00 Para Toluene Sulfonic Acid 2.00 Toluene Loss 10.00 Isopropyl Alcohol 300.00 Effluent Water 425.98 Water 400.00 (Water-400,Generated water-
15.98, para Toluene Sulfonic acid-2, Toluene-8)
Organic Residue 36.02 Process residue-24.02
Distillation residue-12 (Toluene-7, Isopropyl alcohol-5)
Total 1510.00 Total 1510.00
Manufacturing Process Page 34
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Atorvastatin Calcium Stage-5
Batch Size:200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-4 268.00 Stage-5 210.00 Sulfuric Acid 2.50 Mixed Solvent Rceovery
(Methanol + Acetone-23.58,Tert-butanol-30.28)
433.86
Methanol 400.00 Methanol Loss 8.00 Water 300.00 Effluent Water 288.03 (Water-285.53,Sulfuric acid-2.5) 0 Organic residue 30.61 Process residue -18.61
Distillation residue-12 (Methanol-12)
Total 970.5 Total 970.50
Material Balance of Atorvastatin Calcium Stage-6
Batch Size:200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-5 210.00 Atorvastain Calcium 200.00 Calcium Acetate 18.48 Acetic acid Recovery 11.13 Isopropyl Alcohol 400.00 Isopropyl Alcohol Recovery 380.00 Activated Carbon 10.00 Isopropyl Alcohol Loss 20.00 Spent Carbon Recovery 10.00 Organic residue 17.35 Process residue-17.35 Total 638.48 Total 638.48
Manufacturing Process Page 35
ToR Amendment Tagoor Chemicals Private Limited
BUPROPION
Route of synthesis:
Stage-1
1-(3-Chloro-phenyl)-propan-1-one undergoes Bromination with in presence of MDC and Water to give Stage-1 Product.
Stage-2
Stage-1 product undergoes condensation with tertiary-Butyl amine in presence of Toluene and Ethyl acetate to give Bupropion.
Route of synthesis:
Stage-1
ClO
CH3
1-(3-Chloro-phenyl)-propan-1-one
C9H9ClO168.62
+ Br2
159.81
MDCWater
Br
OCl
3-Bromo-1-(3-chloro-phenyl)-propan-1-one
C9H8BrClO247.52
+ HBr
80.91
Stage-2
Br
OCl
3-Bromo-1-(3-chloro-phenyl)-propan-1-one
C9H8BrClO247.52
+ HBr
80.91
+
Tertiary butylamine
NH2
H3C
CH3
CH3
C4H11N73.14
TolueneEthyl acetate
OH3C
NHCH3
CH3
H3CCl
C13H18ClNO239.74
BUPROPION
Manufacturing Process Page 36
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart:
Stage-1
Stage-2
1-(3-Chloro-phenyl)-propan-1-oneLiquid BromineAcetic acidMDC
Acetic acid RecoveryMDC RecoveryEffluent water
Stage-1teritiary-Butyl amineTolueneEthyl acetate
Toluene RecoveryEthyl acetate RecoveryEffluent water
BUPROPION
Material Balance:
Material Balance of Bupropion Stage-1
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 1-(3-Chloro-phenyl)-propan-1-one 175.000 Stage-1 230.000
Liquid Bromine 165.70 Acetic acid Recovery 285.00 Acetic acid 300.00 Acetic acid loss 10.00 MDC 250.00 MDC Recovery 238.00 Water 400.00 MDC loss 8.00 Effluent water 400.00 (Water-400) 0 Process emission 83.82 (Hydrogen bromide – 83.82) 0 Organic residue 35.88 Process residue – 26.88
Distillation residue-9 (Aceticacid-5,MDC-4)
Total 1290.70 Total 1290.70
Manufacturing Process Page 37
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Bupropion Stage-2
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 230.00 Bupropion 200.00 teritiary-Butyl amine 68.00 Toluene Recovery 190.00 Toluene 200.00 Toluene loss 5.00 Ethyl acetate 200.00 Ethyl acetate Recovery 190.00 Water 300.00 Ethyl acetate loss 5.00 Effluent water 306.00 (water-300, Toluene-3, ethyl
acetate-3) 0
Process emission 74.98 (Hydrogen bromide – 74.98) 0 Organic residue 27.02 Process residue -23.02
Distillation residue-4 (Ethyl acetate-2,Toluene-2)
Total 998.00 Total 998.00
CLOPIDOGREL BISULPHATE
Process Description:
Stage-1:
2-Amino-2-(2-chlorophenyl) acetic acid reacts with sulphuric acid and Methanol in presence of Ammonia and Toluene to give Stage-1 Product.
Stage-2:
Stage-1 Product undergoes resolution with L-(+) tartaric acid in presence of Methanol and Acetone to give Stage-2 Product.
Stage-3:
2-(thiophen-2-yl)ethanol reacts with Para Toluene Sulphonyl chloride in presence of Sodium hydrate and Toluene to give Stage-3 Product. Stage-4: Stage-3 Product reacts with Stage-2 product in presence of MDC, Ethyl acetate and Ammonia to give Stage-4 Product.
Manufacturing Process Page 38
ToR Amendment Tagoor Chemicals Private Limited
Stage-5: Stage-4 Product reacts with Formaldehyde, sulphuric acid in presence of Acetone and Sodium bicarbonate to give Stage-5 Product. Stage-6: Stage-5 Product undergoes recrystalisation in presence of Acetone, Acetonitrile and Methanol to give Clopidogrel Bisulphate.
CLOPIDOGREL BISULPHATE Route of Synthesis: Stage-1:
O
OH
Cl
NH2
O
OCH3
Cl
NH2
+ H2SO4
98.08
+ CH3OH
32.04
+
132.14
+
18.02
+
34.06
(NH4)2SO4 H2O
2-Amino-2-(2-chlorophenyl)acetic acid
Methyl 2-amino-2-(2-chlorophenyl)acetate
Ammonium sulphate
2NH3MDC,Toluene
C8H8ClNO2
185.61
C9H10ClNO2
199.63 Stage-2:
O
OCH3
Cl
NH2 + OH
OH O
OH
O
HO
150.09
O
OCH3
Cl
NH2
.OH
OH O
OH
O
HO
Methyl 2-amino-2-(2-chlorophenyl)acetate
L-(+) -Tartaric acid
(S)-Methyl 2-amino-2-(2-chlorophenyl)acetate (2S,3S)-2,3-dihydroxysuccinate
Methanol
C9H10ClNO2
199.63C13H16ClNO8
349.72
C4H6O6
Acetone
Manufacturing Process Page 39
ToR Amendment Tagoor Chemicals Private Limited
Stage-3:
S
OH + H3C
SO
O Cl
SO S
O
OCH3
+ NaOH
40.00
+ NaCl
58.44
+ H2O
18.02
2-(thiophen-2-yl)ethanol p-Toluene sulphonyl chloride
2-(Thiophen-2-yl)ethyl 4-methylbenzenesulfonate
Toluene
C6H8OS
128.19
C7H7ClO2S
190.65
C13H14O3S2
282.38Stage-4:
NH4+
NH4+
OH
OH O
O-
O
-O
+
HCl
36.46
NH3
34.06
2+
SO S
O
OCH3
+
SHN
OCH3O
Cl .HCl +
184.15
+ CH3
SO
O OK
K2HPO4
174.18
+
+ KH2PO4
136.09
210.29
2-(Thiophen-2-yl)ethyl 4-methylbenzenesulfonate
Dipotassoium ortho phosphate
(S)-Methyl 2-(2-chlorophenyl)-2-((2-(thiophen-2-
yl)ethyl)amino)acetate hydrochloride
Ammonium tartarate Potassium salt of p-toluene sulfonic acid
MDC, Ethyl acetate, IPA
Monopotassium phosphate
C13H14O3S2
282.38
C15H17Cl2NO2S
346.27
C4H12N2O6 C7H7KO3S
O
OCH3
Cl
NH2
.OH
OH O
OH
O
HO
(S)-Methyl 2-amino-2-(2-chlorophenyl)acetate Tartarate
C13H16ClNO8
349.72
Manufacturing Process Page 40
ToR Amendment Tagoor Chemicals Private Limited
Stage-5
SHN
OCH3O
Cl .HCl
30.03
+ H2SO4
98.08
S
N
O OCH3
Cl
H2SO4.
CH2O
+ 2H2O
36.03
+ + NaHCO3
84.01
+ NaCl
58.44
+ CO2
44.01
(S)-Methyl 2-(2-chlorophenyl)-2-((2-(thiophen-2-yl)ethyl)amino)
acetate hydrochloride
Formaldehdye
(S)-Methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno
[3,2-c]pyridin-5(4H)-yl)acetate sulfate
Acetone, MDC
C15H17Cl2NO2S
346.27
C16H18ClNO6S2
419.90
Stage-6
S
N
O OCH3
Cl
H2SO4.
Clopidogrel bi sulphate(Crude)
S
N
O OCH3
Cl
H2SO4.
Clopidogrel bi sulphate(pure)
Acetonitrile,Methanol,Acetone
C16H18ClNO6S2
419.90C16H18ClNO6S2
419.90
Manufacturing Process Page 41
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart:
Stage-1
Stage-2
2-Amino-2-(2-chlorophenyl)acetic acidSulphuric acidMethanolLiq. AmmoniaMDCTolueneSodium sulphate
MDC recoveryToluene recovery
Stage-1L-(+)-Tartaric acidMethanol Acetone
Methanol recoveryAcetone recovery
2-(thiophen-2-yl)ethanolPTSCSodium hydroxideSodium sulphateToluene
Stage-3 Toluene Recovery
Stage-2Stage-3(intermediate-1)Liq. AmmoniaHydrochloric acidMDCIPAEthyl acetateActivated carbonHyflowSodium sulfate
Stage-4IPA RecoveryMDC RecoveryEthyl acetate recovery
Stage-5
Stage-6
Stage-4FormaldehydeSulfuric acidSodium bi carbonateAcetoneMDCActivated carbonSodium sulfate
MDC recoveryAcetone recovery
Stage-5Acetone MethanolAcetonitrile
Methanol recoveryAcetone recoveryAcetonitrile Recovery
Clopidogrel Bisulphate
Manufacturing Process Page 42
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of Clopidogrel Bisulphate Stage-1 Batch Size: 200.0 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
2-Amino-2-(2-chlorophenyl)acetic acid 149.00 Stage-1 150.00
Sulphuric acid 78.50 Methylene Dichloride Recovery 475.00 Methanol 25.50 Methylene Dichloride Loss 15.00 Liq. Ammonia 27.50 Toluene Recovery 285.00 Methylene Dichloride 500.00 Toluene loss 7.00 Toluene 300.00 Inorganic solid waste 20.00 Sodium sulphate 20.00 (Sodium sulfate-20) 0
By products (Ammonium sulphate)
105.94
Water 400.00 Effluent water 418.47
(Water-400,Generated water-14.47,Toluene-4)
Organic Residue 24.09
Process Residue-15.09
Distillation Residue-9 (MDC-5,Toluene-4)
Total 1500.50 Total 1500.50
Material Balance of Clopidogrel Bisulphate Stage-2 Batch Size: 200.0 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-1 150.00 Stage-2 247.00 L-(+)-Tartaric acid 112.65 Methanol Recovery 475.00 Methanol 500.00 Methanol loss 15.00 Acetone 150.00 Acetone Recovery 143.00 Acetone loss 5.00 Organic residue 27.65
Process residue-15.65,
Distillation residue-12 ( Methanol-10,Acetone-2)
Total 912.65 Total 912.65
Material Balance of Clopidogrel Bisulphate Stage-3 Batch Size: 200.0 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
2-(thiophen-2-yl)ethanol 97.00 Stage-3 199.00 ParaTolueneSulfonylChloride 144.50 Toluene Recovery 333.00
Manufacturing Process Page 43
ToR Amendment Tagoor Chemicals Private Limited
Sodium hydroxide 30.20 Toluene loss 7.00 Sodium sulphate 10.00 Effluent water 262.71
Toluene 350.00 (Water-200,Generated water-13.58, Sodium chloride-44.13, Toluene-5 )
0
Water 200.00 Inorganic residue 10.00 (Sodium sulfate) 0 Organic residue 19.99 Process Residue-14.99
Distillation Residue-5 (Toluene-5)
Total 831.70 Total 831.70
Material Balance of Clopidogrel Bisulphate Stage-4 Batch Size: 200.0 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-3 199.00 Stage-4 185.00 Stage-2 247.00 MDC Recovery 380.00 Liq. Ammonia 23.80 MDC loss 8.00 Dipotassium ortho phosphate 122.50 IPA Recovery 333.00 Hydrochloric acid 25.68 IPA loss 7.00 MDC 400.00 Ethyl acetate Recovery 380.00 IPA 350.00 Ethyl acetate loss 8.00 Ethyl acetate 400.00 Effluent water 303.72
Activated carbon 2.50 (Water-200, Mono potassium
phosphate-95.72, Ethyl acetate-8)
0
Hyflow 0.50 Spent carbon & Hyflow 3.00 Sodium sulfate 10.00 Inorganic solid waste 10.00 Water 200.00 (Sodium sulfate) 0 Organic residue 363.26 Process Residue-
Organic impurities-59.47 (Ammonium tartarate-129.74, Potassium salt of para-toluene sulfonic acid-148.05, Distillation Residue-26 (MDC-12, IPA-10, Ethyl acetate-4)
Total 1980.98 Total 1980.98
Manufacturing Process Page 44
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Clopidogrel Bisulphate Stage-5 Batch Size: 200.00 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-4 185.00 Stage-5 210.00 Formaldehyde 16.00 MDC Recovery 665.00 Sulfuric acid 53.00 MDC loss 15.00 Sodium bi carbonate 44.75 Acetone Recovery 570.00 Acetone 600.00 Acetone loss 12.00 MDC 700.00 Effluent water 350.32
Activated carbon 10.00 (Water-300, Generated water-19.24,Sodium chloride-31.08)
Sodium sulfate 20.00 Process emission 23.49 Water 300.00 (Carbon dioxide-23.49) Spent carbon 10.00 Inorganic solid waste 20.00 (Sodium sulfate) Organic residue 52.94 Process Residue-14.94,
Distillation Residue-38 ( MDC-20, Acetone-18 )
Total 1928.75 Total 1928.75
Material Balance of Clopidogrel Bisulphate Stage-6 Batch Size: 200.00 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-5 210.00 Clopidogrel Bisulphate 200.00 Acetone 250.00 Acetonitrile Recovery 190.00 Methanol 150.00 Acetonitrile Loss 5.00 Acetonitrile 200.00 Acetone Recovery 238.00 Acetone Loss 7.00 Methanol Recovery 143.00 Methanol Loss 5.00
Organic Residue 22.00 Process residue-10,
Distillation residue-12 (Acetonitrile-5,Acetone-5, Methanol-2)
Total 810.00 Total 810.00
Manufacturing Process Page 45
ToR Amendment Tagoor Chemicals Private Limited
CYCLOBENZAPRINE HYDROCHLORIDE
Process Description: Stage-1: 1-bromo-3-chloropropane reacts with Dimethyl amine in presence of Sodium
Hydroxide,Toluene and water to give Steage-1 Product.
Stage-2: Step-A: Phenyl acetic acid reacts with Pthalic anhydride in prrsence of Methanol and sodium acetate to give stage-A product. Step-B: Stage-A Product reacts with Hydrogen in presence of sodium hydroxide and rabey-nickel to give Step-B Product. Step-C: Step-B product undergoes cyclisation in presence of Xylene, P2O5 and Phosphoric acid to give Stage-2 Product. Stage-3: Stage-2 Product reacts with Stage-1 Product in presence of Magnesium, THF,
Toluene and Methanol to give Stage-3 Product.
Stage-4: Stage-3 Product undergoes Dehydration with Hydrochloric acid in presence of
Toluene and Acetone to give Cyclobenzaprine Hydrochloride
Route of Synthesis Stage-1:
Dimethyl amine1-bromo-3-chloropropane
3-chloro-N,N-dimethylpropan-1-amine
Toluene, water, HCl
KOH, Sodium sulphate
NaBr
NaOH
C3H6BrCl
157.44
40.00
C5H12ClN
121.61
102.9
N
CH3
CH3
Cl
HN
CH3H3CClBr + +
+ +
C2H7N
45.08
H2O
18.02
Manufacturing Process Page 46
ToR Amendment Tagoor Chemicals Private Limited
Stage-2:
Step-A:
COOH
Phenyl-acetic acidC8H8O2136.15
+
O
O
OPhthalic anhydride
C8H4O3
148.12
O
O3-Benzylidene-3H-
isobenzofuran-1-oneC15H10O2
222.24
+ H2O18.02
+ CO2
44.01
Step-B:
O
O3-Benzylidene-3H-
isobenzofuran-1-oneC15H10O2
222.24
OH
O2-Styryl-benzoic acid
C15H12O2
224.25
+ H2
2.02
NaOH solution,HCl solution,Raney nickel
Manufacturing Process Page 47
ToR Amendment Tagoor Chemicals Private Limited
Step-C:
OH
O
2-Styryl-benzoic acidC15H12O2
224.25
O
DibenzosuberenoneC15H10O
206.24
P2O5,H3PO4
+ H2O
18.02Xylene
Stage-3:
3-chloro-N,N-Dimethylpropan-1-amine
+Mg+ NH4Cl
C5H12ClN
121.61
C15H10O
206.24
24.31 53.49
+ MgCl2 + NH3
95.21 17.03
THF/Methanol
5-(3-Dimethylamino-propyl)-5H-dibenzo[a,d]cyclohepten-5-ol
C20H23NO293.40
Dibenzosuberenone
N
CH3
CH3
Cl
O
+
OH
N
Manufacturing Process Page 48
ToR Amendment Tagoor Chemicals Private Limited
Stage-4:
+ HCl
36.46
Acetone
Carbon
+ H2O
18.025-(3-Dimethylamino-propyl)-5H-
dibenzo[a,d]cyclohepten-5-olC20H23NO
293.40
Cyclobenzaprine HydrochlorideC20H22ClN
311.85
OH
N
N
. HCl
Manufacturing Process Page 49
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart
Stage-1
Stage-2
Stage-3
CYCLOBENZAPRINE HYDROCHLORIDE
1-Bromo-3-Chloro propaneDi methyl amineTolueneSodium HydroxideHydrochloric AcidPotassium hydroxideSodium sulfate.
Toluene RecoveryEffluent water
Phenyl acetic acidPthalic anhydrideSodium acetate tri hydrateMethanolRaney NickelSodium Hydroxide SolutionHydrochloric acid SolutionTolueneHydrogen gasPhosphoric acidO-XylenePhosphorous penta oxide
Toluene RecoveryMethanol RecoveryEffluent water
Stage-2Stage-1Magnesium Ethyl BromideAmmonium ChlorideSodium Hydroxide (10%)Dil Hydrochloric Acid Tetra hydra furanTolueneMethanol
Toluene RecoveryMethanol RecoveryEffluent water
Stage-2Hydrochloric AcidActivated CarbonAcetoneTolueneIPA IPA HCl
IPA RecoveryAcetone RecoveryEffluent water
Stage-4
Manufacturing Process Page 50
ToR Amendment Tagoor Chemicals Private Limited
Material Balance
Material Balance of Cyclobenzaprine Hydrochloride Stage-1 BatchSize:200 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
1-Bromo-3-Chloro propane 123.00 Stage-1 90.00 Di methyl amine 35.20 Toluene Recovery 232.00 Toluene 250.00 Toluene Loss 12.00 Sodium Hydroxide 31.25 Effluent Water 520.02 Hydrochloric Acid 10.00 (water-500, Generated water-
14.02 , potassium hydroxide- 5, Toluene-1)
0
Potassium hydroxide 5.00 By product (Sodium Bromide-80.32,)
80.32
Sodium sulfate. 5.00 Inorganic solid waste 5.00 Water 500.00 (Sodium sulfate) 0 Organic Residue 20.11 (Process residue-15.11,
Distillation residue -5 (Toluene-5)
Total 959.45 Total 959.45
Material balance of Cyclobenzaprine Hydrochloride Stage-2 Batch Size: 500.00 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Phenyl acetic acid 71.00 Stage-2 90.00 Pthalic anhydride 77.20 Methanol recovery 475.00 Sodium acetate tri hydrate 10.00 Methanol Loss 15.00 Methanol 500.00 Toluene recovery 475.00 Raney Nickel 5.00 Toluene Loss 10.00
Sodium Hydroxide Solution 100.00 O-Xylene Recovery 475.00
Hydrochloric acid Solution 50.00 O-Xylene Loss 25.00 Toluene 500.00 Raney Nickel Recovery 5.00 Hydrogen gas 1.00 Effluent water 875.69
Phosphoric acid 50.00 (Water-600,Generated water-17.69,Toluene-8,Sodium hydroxide Solution-100,HydroChloroc acid-50,Phosphaorous pentoxide-50,Phosphoric acid-50)
0
O-Xylene 500.00 Process emission 22.93
Phosphorous penta oxide 50.00 (Carbon dioxide-22.93) 0
Manufacturing Process Page 51
ToR Amendment Tagoor Chemicals Private Limited
Water 600.00 Organic residue 45.58
Process residue -28.58 Distillation residue-17 (Methanol-10,Toluene-7)
Total 2514.20 Total 2514.20
Material Balance of Cyclobenzaprine Hydrochloride Stage-3 BatchSize:200 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-2 150.00 Stage-2 200.00 Stage-1 90.00 Toluene Recovery 104.00 Magnesium 18.00 Toluene Loss 6.00 Ethyl Bromide 1.00 Methanol Recovery 187.00 Ammonium Chloride 40.00 Methanol Loss 10.00 Sodium Hydroxide (10%) 100.00 THF Recovery 283.00 Dil Hydrochloric Acid 9.00 THF Loss 15.00 Tetra hydra furan 300.00 Effluent Water 904.40 Toluene 120.00 (water-800, Sodium chloride-
14.4, water from NaOH-90) 0
Methanol 200.00 By product (Magnesium Chloride-69.24,)
69.24
Water 800.00 Process Emission 12.38 (Ammonia-12.38) 0 Organic Residue 36.98 Process residue-21.98
Distillation residue-15 (Toluene-10,Methanol-3,THF-2)
Total 1828 Total 1828
Material Balance of Cyclobenzaprine Hydrochloride Stage-4 BatchSize:200Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-2 200.00 Cyclobenzaprine Hydrochloride 200.00 Hydrochloric Acid 25.00 Toluene Recovery 698.00 Activated Carbon 20.00 Toluene Loss 37.00 Acetone 250.00 Acetone Recovery 237.00 Toluene 750.00 Acetone Loss 12.00 IPA 1200.00 IPA Recovery 1152.00 IPA HCl 10.00 IPA Loss 58.00 Water 800.00 Effluent Water 823.28
Manufacturing Process Page 52
ToR Amendment Tagoor Chemicals Private Limited
(Water-800,generated water-18.28, Toluene-5)
Spent Carbon 20.00 Organic Residue 17.72 Process residue-6.72
Distillation residue -11 (Toluene-10,Acetone-1)
Total 3255.00 Total 3255.00
CYPROHEPTADINE HYDROCHLORIDE Process Description:
Stage-1:
Step-A:
Phenyl acetic acid reacts with Pthalic anhydride in prrsence of Methanol and sodium acetate to give stage-A product.
Step-B:
Stage-A Product reacts with Hydrogen in presence of sodium hydroxide and rabey-nickel to give Step-B Product.
Step-C:
Step-B product undergoes cyclisation in presence of Xylene, P2O5 and Phosphoric acid to give Stage-1 Product.
Stage-2:
Stage-1 Product undergoes Hydrogenation with hydrogen in presence of Methanol and Raney Nickel to give Stage-2 Product.
Stage-3:
Stage-2 Product undergoes Chlorination with Thionyl chloride in presence of Toluene, Chloform and Sodium Hydroxide to give stage-3 Product.
Stage-4:
Stage-3 product reacts with N-methyl-4-Chloro Piperidine in presnec of Magnesium, THF, Methanol, Toluene and Ammonia to give Staeg-4 product.
Stage-5:
Manufacturing Process Page 53
ToR Amendment Tagoor Chemicals Private Limited
Stage-4 product undergoes Dehydration in presence of Hydrochloric acid, Toluene,
IPA and water to give Cyproheptadine Hydrochloride
Route of Synthesis:
Stage-1
Step-A:
COOH
Phenyl-acetic acidC8H8O2136.15
+
O
O
OPhthalic anhydride
C8H4O3
148.12
O
O3-Benzylidene-3H-
isobenzofuran-1-oneC15H10O2
222.24
+ H2O18.02
+ CO2
44.01
Step-B:
O
O3-Benzylidene-3H-
isobenzofuran-1-oneC15H10O2
222.24
OH
O2-Styryl-benzoic acid
C15H12O2
224.25
+ H2
2.02
NaOH solution,HCl solution,Raney nickel
Manufacturing Process Page 54
ToR Amendment Tagoor Chemicals Private Limited
Step-C:
OH
O
2-Styryl-benzoic acidC15H12O2
224.25
O
DibenzosuberenoneC15H10O
206.24
P2O5,H3PO4
+ H2O
18.02Xylene
Stage-2:
N-Methyl4-piperidone
N
O
CH3
C6H11NO
113.16
+ H2
2.02
Methanol
N-Methyl 4-Hydroxy piperidine
N
OH
CH3
C6H13NO
115.17
Stage-3:
SOCl2+ + NaOH+ SO2NaCl +
N-Methyl-4-Hydroxy piperidine
N-Methyl-4-chloro piperidine
Na2CO3
TolueneChloroform
N
OH
CH3
C6H13NO
115.17
40.0118.97
N
Cl
CH3
C6H12ClN133.62
58.564.06
+
18.0
H2O
Manufacturing Process Page 55
ToR Amendment Tagoor Chemicals Private Limited
Stage-4:
O
DibenzosuberenoneC15H10O
206.24
++ Mg + NH4Cl
24.31 53.49
+ MgCl2 + NH3
95.21 17.03
THF/Methanol
OH
C21H23NO305.41
N-Methyl-4-Chloro Piperidine
N
Cl
CH3
C6H12ClN
133.62
N
5-(1-Methyl-piperidin-4-yl)-5H-dibenzo[a,d]cyclohepten-5-ol
Stage-5:
Step-A:
OH
C21H23NO
305.41
N
5-(1-Methyl-piperidin-4-yl)-5H-dibenzo[a,d]cyclohepten-5-ol
+ HCl + 1 1/2H2O N
4-(5H-dibenzo[a,d][7]annulen-5-ylidene)-1-methylpiperidine hydrochloride
Sesquihydrate
H
Cl
1 1/2H2O
36.46 27.0
C21H21N·HCl·1.5H2O350.86
+ H2O
18.02
Manufacturing Process Page 56
ToR Amendment Tagoor Chemicals Private Limited
Step-B:
N
4-(5H-dibenzo[a,d][7]annulen-5-ylidene)-1-methylpiperidine hydrochloride
Sesquihydrate
H
Cl
1 1/2H2O
C21H21N·HCl·1.5H2O
350.86
N
Cyproheptadine HClsesquihydrate
H
Cl
1 1/2H2O
C21H21N·HCl·1.5H2O
350.86
IPA HCl
Flowchart:
Stage-1
Stage-2
Stage-3
Phenyl acetic acidPthalic anhydrideSodium acetate tri hydrateMethanolRaney NickelSodium Hydroxide SolutionHydrochloric acid SolutionTolueneHydrogen gasPhosphoric acidO-XylenePhosphorous penta oxide
Toluene recoveryMethanol recoveryEffluent water
N -Methyl-4-PiperidoneHydrogen Methanol
Methanol recoveryEffluent water
Stage-2Thionyl chlorideSodium HydroxideSodium bicarbonateToluene Chloroform
Toluene RecoveryChloroform RecoveryEffluent Water
Stage-1MagnesiumLithium bromideN-methyl-4-Chloro piperidineEthyl bromideAmmonium ChlorideTetrahydrafuranMethanolToluene
Toluene RecoveryMethanol RecoveryEffluent water
Stage-4IPAHCl(30%)
IPA RecoveryEffluent water
Stage-4
Stage-5
CYPROHEPTADINE HYDROCHLORIDE
Manufacturing Process Page 57
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material balance of Cyproheptadine Hydrochloride Stage-1 Batch Size: 500.00 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Phenyl acetic acid 260.00 Stage-1 332.00 Pthalic anhydride 283.00 Methanol recovery 475.00 Sodium acetate tri hydrate 10.00 Methanol Loss 15.00 Methanol 500.00 Toluene recovery 475.00 Raney Nickel 5.00 Toluene Loss 10.00 Sodium Hydroxide Solution 100.00 O-Xylene Recovery 475.00 Hydrochloric acid Solution 50.00 O-Xylene Loss 25.00 Toluene 500.00 Raney Nickel Recovery 5.00 Hydrogen gas 4.00 Effluent water 922.82 Phosphoric acid 50.00 (Water-600,Generated
water-64.82,Toluene-8,Sodium hydroxide Solution-100,HydroChloroc acid-50,Phosphaorous pentoxide-50,Phosphoric acid-50)
O-Xylene 500.00 Process emission 84.00 Phosphorous penta oxide 50.00 (Carbon dioxide-84) Water 600.00 Organic residue 93.18 Process residue -76.18
Distillation residue-17 (Methanol-10,Toluene-7)
Total 2912 Total 2912.00
Material Balance of Cyproheptadine Hydrochloride Stage-2 BatchSize:500Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
N –Methyl-4-Piperidone 205.00 Stage-2 200.00 Hydrogen 4.00 Methanol Recovery 570.00 Methanol 600.00 Methanol Loss 12.00 Water 800.00 Effluent Water 800.00 (Water-800) Organic residue 27.00 Process residue-9
Distillation residue-18 (Methanol-18)
Total 1609.00 Total 1609.00
Manufacturing Process Page 58
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Cyproheptadine Hydrochloride Stage-3 BatchSize:500Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-2 200.00 Stage-3 216.00 Thionyl chloride 207.00 Toluene Recovery 570.00 Sodium Hydroxide 70.00 Toluene Loss 12.00 Sodium bicarbonate 20.00 Chloroform Recovery 475.00 Toluene 600.00 Chloroform Loss 25.00 Chloroform 500.00 Effluent Water 963.26 Water 800.00 (Water-800,Sodium chloride-
102,Generated water-31.26,Toluene-10,Sodium bicarbonate-20)
Process emission 111.24 (Sulphur dioxide-111.24) 0 Organic residue 24.50 Process residue-16.5
Distillation residue-8 (Toluene-8)
Total 2397.00 Total 2397.00
Material Balance of Cyproheptadine Hydrochloride Stage-4 BatchSize:500Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-1 332.00 Stage-4 462.00 Magnesium 40.00 THF Recovery 331.00 Lithium bromide 5.00 THF Loss 17.00 N-methyl-4-Chloro piperidine 216.00 Methanol Recovery 190.00 Ethyl bromide 1.00 Methanol Loss 10.00 Ammonium Chloride 87.00 Toluene Recovery 774.00 Tetrahydrafuran 350.00 Toluene Loss 40.00 Methanol 200.00 Effluent Water 1506.00 Toluene 820.00 (Water-1500, ,Lithium Bromide-
5,Ethyl Bromide-1,Toluene-3)
Water 1500.00 Process Emission (Ammonia-27.41)
27.41
By product (Magnesium Chloride-153.26)
156.26
Manufacturing Process Page 59
ToR Amendment Tagoor Chemicals Private Limited
Organic Residue 37.33 Process residue-33.33
Distillation residue-4 ( Toluene-2,THF-2)
Total 3551.00 Total 3551.00
Material Balance of Cyproheptadine Hydrochloride Stage-5 BatchSize:500Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-4 462.00 Cyproheptadine Hydrochloride 500.00 IPAHCl(30%) 786.00 IPA Recovery 570.00 Water 800.00 IPA Loss 12.00 Effluent Water 916.26 (Water-759,generated water-
27.26,water from HCl-130)
Organic residue 49.74 Process residue-31.74
Distillation residue- (IPA-18)
Total 2048.00 Total 2048.00
DESLORATADINE
Process Description:
Stage-1
3-[2-(3-chlorophenyl)-ethyl] pyridine-2-carbonitrile reacts with Potassium hydroxide, Hydrochloric acid in presence of n-Butanol to give Stage-1 product.
Stage-2
Staeg-1 product undergoes cyclisation with Phosphorous penta chloride to give Stage-2 product.
Stage-3
Stage-2 product reacts with 4-Chloro-1-methyl piperdine, Magnesium, Hydrochloric acid in the presence of THF to give Stage-3 product.
Stage-4
Stage-3 Product undergoes dehydaration with Sulfuric acid and Sodium Hydroxide in presence of Ethyl acetate and n-Hexane to give Stage-4 product.
Manufacturing Process Page 60
ToR Amendment Tagoor Chemicals Private Limited
Stage-5
Stage-4 product reacts with ethyl chloro formate in the presence of Toluene and Cyclo hexane to give Stage-5 product.
Stage-6
Stage-5 product reacts with Sodium hydroxide, Hydrochloric acid in the presence of Methanol to give Desloratadine .
DESLORATADINE
Route of Synthesis:
Stage-1:
N CN
Cl
3-[2-(3-Chlorophenyl)-ethyl]-pyridine-2-carbonitrile
C14H11ClN2
242.70
+ KOH
56.11
+ H2O
18.0
+2HCl
N COOH
Cl
3-[2-(3-Chloro-phenyl)-ethyl]-pyridine-2-carboxylic acid
C14H12ClNO2
261.70
+ KCl
74.55
+ NH4Cl
53.49
72.00
Stage-2:
N COOH
Cl
3-[2-(3-Chloro-phenyl)-ethyl]-pyridine-2-carboxylic acid
C14H12ClNO2
261.70
PCl5 N
Cl
O+ H2O
8-Chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one
C14H10ClNO
243.69
18.0
Manufacturing Process Page 61
ToR Amendment Tagoor Chemicals Private Limited
Stage-3:
N
Cl
O8-Chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one
C14H10ClNO
243.69
+
4-Chloro-1-methyl-piperidine
N Cl
C6H12ClN
133.62
+ Mg
Magnesium
24.31
+ HCl
Hydrochloric acid36.5
N
Cl
N
CH3
OH
THF
8-Chloro-11(1-methyl-piperidine-4-yl)-6,11-dihydro-5H-benzo[5,6]cyclohepta
[1,2-b]pyriidn-11-olC20H23ClN2O
342.86
+ MgCl2
95.21
Manufacturing Process Page 62
ToR Amendment Tagoor Chemicals Private Limited
Stage-4:
N
Cl
N
CH3
OH
8-Chloro-11(1-methyl-piperidine-4-yl)-6,11-dihydro-5H-benzo[5,6]cyclohepta
[1,2-b]pyriidn-11-olC20H23ClN2O
342.86
H2SO4
N
Cl
N
CH3
8-Chloro-11(1-methyl-piperidine-4-yl)-6,11-dihydro-5H-benzo[5,6]cyclohepta
[1,2-b]pyridine
C20H21ClN2
324.85
+ 3 H2O
54.06
[N-Methyl Desloratadine]
+ + 2 NaOH
98.08 80.00
Ethyl acetate
n-Hexane
Na2SO4
142.04
+
Manufacturing Process Page 63
ToR Amendment Tagoor Chemicals Private Limited
Stage-5:
N
Cl
N
CH3
8-Chloro-11(1-methyl-piperidine-4-yl)-6,11-dihydro-5H-benzo
[5,6]cyclohepta[1,2-b]pyridine
C20H21ClN2
+
[N-Methyl Desloratadine]
Ethyl chloroformateC3H5ClO2
108.52
Toluene
N
Cl
N
COOC2H5
4-(8-Chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)
-piperidine-1-carboxylic acid ethyl ester
C22H23ClN2O2
382.88
+ CH3Cl
50.49
O
O Cl
Chlormethane324.85
Stage-6:
N
Cl
N
COOC2H54-(8-Chloro-5,6-dihydro-benzo[5,6]
cyclohepta[1,2-b]pyridin-11-ylidene)-piperidine-1-carboxylic acid ethyl ester
C22H23ClN2O2
382.88
+ NaOH
40.0
+ HCl
36.46
10 % Aq.MeOH
N
Cl
N
H
+ C2H5OH
46.07
+ NaCl
58.5
+ CO2
44.0
Desloratadine
C19H19ClN2
310.82
Manufacturing Process Page 64
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart:
3-[2-(3-Chloro phenyl)-ethyl]-pyridine-2-carbonitrilePotassium hydroxideHydrochloric acid
Stage-1 Ammonium chloride
Stage-2 DCM RecStage-1Phosphorous pentachlorideDCM
Stage-3 THF RecStage-24-Chloro-1-methyl-piperidineTHF
Stage-4 Generated waterStage-3Sulfuric acid
Stage-5 Toluene RecStage-4Ethyl chloroformateToluene
Stage-6 Methanol RecStage-5Sodium hydroxideMethanol
DESLORATADINE
Manufacturing Process Page 65
ToR Amendment Tagoor Chemicals Private Limited
Material Balance
Material Balance of Desloratadine Stage-1
Batch Size: 200.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 3-[2-(3-Chlorophenyl)-ethyl]-pyridine-2-carbonitrile 296.00 Stage-1 287.00
Potassium hydroxide 68.50 n-Butanol Recovery 90.00 n-Butanol 100.00 n-Butanol Loss 10.00 Hydrochloric acid 87.50 Effluent water 478.10 Water 500.00 (Water-478.10,) By products
(Potassium chloride-90.87, Ammonium chloride-65.12)
155.99
Organic Residue 30.91 Total 1052 Total 1052
Material Balance of Desloratadine Stage-2
Batch Size: 200.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 287.00 Stage-2 240.00 Methylene dichloride 200.00 Methylene dichloride Recovery 190.00 Phosphorous Pentachloride 228.00 Methylene dichloride Loss 10.00 Hydrochloric acid 30.00 Ethyl acetate Recovery 475.00 Ethyl acetate 500.00 Ethyl acetate Loss 10.00 Activated carbon 5.00 n-Hexane Recovery 90.00 Hyflow 5.00 n-Hexane Loss 5.00 n-Hexane 100.00 Spent carbon & Hyflow Recovery 10.00 water 300.00 Effluent water 585.50
(Water-300, Generated water-19.50, Hydrochloric acid-30, Ethyl acetate-8, Phosphorous Pentachloride -228)
Organic Residue 39.50
Process residue -27.50
Distillatiojn residue-12 (n-Hecxane-5, Ethyl acetate-7)
Total 1655.00 Total 1655.00
Manufacturing Process Page 66
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Desloratadine Stage-3
Batch Size: 200.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 240.00 Stage-3 304.00 4-chloro-1-methyl-piperidine 131.50 Tetrahydrofuran Recovery 475.00 Tetrahydrofuran 500.00 Tetrahydrofuran Loss 15.00 Magnesium metal 23.75 EthyleneDiBromide Recovery 90.00 EthyleneDiBromide 100.00 EthyleneDiBromide Loss 10.00 Ethyl acetate 500.00 Ethyl acetate Recovery 475.00 n-Hexane 100.00 Ethyl acetate Loss 10.00 Acetonitrile 150.00 Acetonitrile Recovery 143.00 Isopropyl alcohol 100.00 Acetonitrile Loss 7.00 Hydrochloric acid 35.75 Isopropyl alcohol Recovery 95.00 Water 500.00 Isopropyl alcohol Loss 5.00 n-Hexane Recovery 90.00 n-Hexane Loss 3.00 Effluent water 520.00
(Water-500,
THF-10, Ethyl acetate-8, n-Hexane-2)
By products (Magnesium chloride) 93.60
Organic Residue 45.40
Process residue-33.40
Distillation residue-12 (n-Hexane-5, Ethyl acetate-7)
Total 2381.00 Total 2381.00
Manufacturing Process Page 67
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Desloratadine Stage-4
Batch Size: 200.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 304.00 Stage-4 259.00 Sulphuric acid 88.00 Ethyl acetate Recovery 475.00 Ethyl acetate 500.00 Ethyl acetate Loss 10.00 Sodium hydroxide 70.85 n-Hexane Recovery 475.00 n-Hexane 500.00 n-Hexane Loss 25.00 Hyflow 5.00 Effluent water 678.57
Activated carbon 2.00 (Water-500, generated water-47.72, Sodium sulfate-125.85,Ethyl acetate-5
water 500.00 Spent carbon & Hyflow Recovery 7.00 Organic Residue 40.28
Process residue -30.28
Distillation residue (Ethyl acetate-10)
Total 1969.85 Total 1969.85
Material Balance of Desloratadine Stage-5
Batch Size: 200.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-4 259.00 Stage-5 274.00 Triethyl amine 80.00 Toluene Recovery 475.00 Ethyl chloro formate 86.50 Toluene Loss 10.00 Cyclo hexane 400.00 Cyclohexane Recovery 380.00 Toluene 500.00 Cyclohexane Loss 20.00 Water 400.00 Effluent water 488.00 (Water-400, Triethylamine-80,
,Toluene-8)
Process emission 40.14 (Chloro Methane-40.14) Organic Residue 38.36
Process residue-31.36
Distillation residue – 7 (Toluene-7)
Total 1725.50 Total 1725.50
Manufacturing Process Page 68
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Desloratadine Stage-6
Batch Size: 200.0Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-5 274.00 Desloratadine 200.00
Sodium hydroxide flakes 28.50 Methanol Recovery+ ethanol-32.88
270.88
Methanol 250.00 Methanol Loss 12.00 Toluene 300.00 Toluene Recovery 285.00 Cyclo hexane 400.00 Toluene Loss 10.00 Activated carbon 3.00 Cyclo hexane Recovery 380.00 Hydrochloric acid 26.00 Cyclo hexane Loss 20.00 water 500.00 Effluent water 544.64
(Water-500,Toluene-3,Sodium Chloride-41.64)
Process Emissions 31.23 (Carbon dioxide-31.23) Spent carbon 3.00 Organic Residue 24.75
Process residue -22.75
Distillation residue- (Toluene-2)
Total 1781.50 Total 1781.50
DOMPERIDONE MALEATE
Process Description: Stage-1 5-Chloro-1-{1-[3-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-propyl]-piperidin-4-yl}-
1,3-dihydro-benzoimidazol-2-one(Domeperidone) Product reacts with Maleic
acid Product in presence of Methanol to give Domperidone Maleate
Manufacturing Process Page 69
ToR Amendment Tagoor Chemicals Private Limited
Route of synthesis: Stage-1:
NH
N ON
NH
N
O
Cl
425.91
(Domperidone)C22H24ClN5O2
Maleic acid
O
OH
O
OH
C4H4O4
116.07
+
5-Chloro-1-{1-[3-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-propyl]-piperidin-4-yl}-1,3-
dihydro-benzoimidazol-2-one
NH
NO
NNH
N
O
Cl
O
OH
O
OH
Domperidone Maleate
C26H28ClN5O6
541.98
Methanol
Manufacturing Process Page 70
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-10 Methanol Recovery
5-Chloro-1-{1-[3-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-propyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one(Domeperidone)Maleic acidMethanol
DOMPERIDONE MALEATE
Material Balance:
Material balance of Domperidone Maleate Stage-1
Batch Size:500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 5-Chloro-1-{1-[3-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-propyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one(Domeperidone)
400.00 Domperidone Maleate 500.00
Maleic acid 110.00 Methanol Recovery 475.00 Methanol 500.00 Methanol Loss 15.00 Organic residue 20.00 Process residue-10
Distillation residue-10 (Methanol)
Total 1010.00 Total 1010.00
Manufacturing Process Page 71
ToR Amendment Tagoor Chemicals Private Limited
DOMPERIDONE
Process description Stage-1 Methyl acrylate reacts with Methylamie in presence fo Methanol to give Stage-1
product
Stage-2 Step-A Stage-1 product reacts with Sodium methoxide in presence of water and
Chloroform to give Step-A product
Step-B Step-A product undergoes Hydrolysis with water in presence of Chloroform to
give Stage-2 Product
Stage-3 Stage-2 product reacts with Ethylchkloroformate in presence of Toluene to give
Stage-3 product
Stage-4 Step-A Stage-3 product undergoes Hydrogenation with Hydrogen gas in presence of
Raney Nickel and Methanol to give Step-A product
Step-B
Step-A product undergoes Amination with Ammonium and Sulphuric acid in
presence of Methanol to give Stage-4 product .
Stage-5 Stage-4 product undergoes Condensation with 1, 4-Dichloro-2-nitrobenzene in
presence of Water and Soda Ash to give Stgae-5 product
Stage-6 Stage-5 product undergoes Hydrogenation with Hydrogen in presence of Raney
Nickel and Methanol to give Stage-6 product
Stage-7 Step-A
Manufacturing Process Page 72
ToR Amendment Tagoor Chemicals Private Limited
Stage-6 product reacts with Urea in presence of Water and Ammonium
hydroxide to give Step-A product
Step-B Step-A product undergoes Hydrolysis with Water and Soduium hydroxide in
presence of Water to give Stage-7 product
Stage-8 Orthophenylene diamie reacts with Methylacetoacetate in presence of O-
Xylene , Sodium hydroxide and water to give Stage-8 product
Stage-9 Stage-8 product reacts with 1-Bromo-3-Chloro-propane in presence of Sodium
hydroxide , TBAB & Water to give Stage-9 product
Stage-10 Stage-9 product reacts with Hydrochloric acid in presence of Methanol to give
Stage-10 product
Stage-11 Stage-7 product condensed with Stage-10 product in presence of Ammonium
hydroxide and MIBK to give Domperidone product
Route of synthesis: Stage-1
Methyl acrylateC4H6O2
2X86.09=172.18
CH3
NH2+
Methylamine31.06
CH3N
OO
CH3
OO
CH33-[(2-Methoxycarbonyl-ethyl)-methyl-amino]-
propionic acid methyl esterC9H17NO4
203.24
Methanol
OO
2
Manufacturing Process Page 73
ToR Amendment Tagoor Chemicals Private Limited
Stage-2 Step-A
CH3N
OO
CH3
OO
CH33-[(2-Methoxycarbonyl-ethyl)-methyl-
amino]-propionic acid methyl esterC9H17NO4
203.24
CH3N
OO
CH3
OCH3
O Na
Sodium 4-methoxy-3-(methoxycarbonyl)-1-methylpiperidin-
4-olateC9H16NNaO4
225.22
Sodium methoxide
CH3ONa+
54.02
+ CH3OH
32.04
Chloroform& water
Step-B:
CH3 N
OO
CH3
OCH3
ONa
Sodium 4-methoxy-3-(methoxycarbonyl)-1-methylpiperidin-
4-olateC9H16NNaO4
225.22
N
O
CH3
N-Methyl-piperidin-4-one
Chloroform
C6H11NO113.16
+ CH3COONa+
82.03
+ CH3OH
32.04
H2O
18.0
+ 1/2 O2
16.0
Distillation
Manufacturing Process Page 74
ToR Amendment Tagoor Chemicals Private Limited
Stage-3:
N-Methyl4-piperidoneC6H11NO
+Toluene
Ethyl chloroformate
O
O Cl
C3H5ClO2
108.52
N
O
O O CH3
4-Oxo-piperidine-1-carboxylic acid
ethyl esterC8H13NO3
171.19
N
O
CH3
113.16
CH3Cl+
50.49
Stage-4: Step-A
N
O
O O CH3
4-Oxo-piperidine-1-carboxylic acid
ethyl esterC8H13NO3
171.19
+ H2
C8H15NO3
173.21
2.02
Raney Nickel &Methanol
N
OH
O O CH3
4-Hydroxy-piperidine-1-carboxylic acid
ethyl ester
Manufacturing Process Page 75
ToR Amendment Tagoor Chemicals Private Limited
Step-B
C8H15NO3
173.21
Methanol
N
OH
O O CH3
4-Hydroxy-piperidine-1-carboxylic acid
ethyl ester
+ 3 NH3
51.09
N
NH2
O O CH3
4-Amino-piperidine-1-carboxylic acid
ethyl esterC8H16N2O2
172.22
+ H2O
18.02
+ H2SO4
98.08
+ (NH4)2SO4
132.14
Stage-5
+
Cl
Cl
NO2
C6H3Cl2NO2
192.00
4-(4-Chloro-2-nitro-phenylamino)-piperidine-1-carboxylic acid ethyl ester
+
C14H18ClN3O4
327.76
Soda AshWater
1,4-Dichloro-2-nitro-benzene
N
NH2
O O CH3
4-Amino-piperidine-1-carboxylic acid
ethyl ester
C8H16N2O2
172.22
N
NH
O O CH3
Cl
O2N
HCl
36.46
Manufacturing Process Page 76
ToR Amendment Tagoor Chemicals Private Limited
Stage-6
4-(4-Chloro-2-nitro-phenylamino)-piperidine-1-carboxylic acid ethyl ester
+
C14H18ClN3O4
327.76
H2
2.02
+
32.00
N
NH
O O CH3
Cl
O2N
O2
Raney NickelMethanol N
NH
O O CH3
Cl
H2N
4-(2-Amino-4-chloro-phenylamino)-piperidine-1-carboxylic acid ethyl ester
C14H20ClN3O2
297.78
Manufacturing Process Page 77
ToR Amendment Tagoor Chemicals Private Limited
Stage-7
Step-A
+
N
NH
O O CH3
Cl
H2N
4-(2-Amino-4-chloro-phenylamino)-piperidine-1-carboxylic acid ethyl ester
C14H20ClN3O2
297.78
Urea
NH2
OH2N
+
CH4N2O
60.06
NH4OH
35.05
+ HCl
36.46
Activated carbon Water
NO
O
CH3
NHN
O
C15H18ClN3O3
323.77
+ NH4Cl
53.49
+ H2O
18.02
+
34.06
2 NH3Cl4-(5-Chloro-2-oxo-2,3-dihydro-benzoimidazol-1
-yl)-piperidine-1-carboxylic acid ethyl ester
Manufacturing Process Page 78
ToR Amendment Tagoor Chemicals Private Limited
Step-B:
C15H18ClN3O3
323.77
4-(5-Chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester
Cl
N
HN O
N
O
O+ NaOH
40.00 5-Chloro-1-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one
+ C2H5ONa
68.05
+ CO2
44.00
C12H14ClN3O251.71
NH
N
O
HN
Cl
Stage-8:
NH2
NH2
ortho phenylene di amine
C6H8N2
108.14
+H3C
O
O
CH3
O
Methyl aceto acetate
C5H8O3
116.12
NH
N
H3CCH2
O
1-Isopropenyl-1,3-dihydro-benzoimidazol-2-one
C10H10N2O
174.2
+ CO2
44.0
3 H2
6.0
O-XyleneWater
+ NaOH
40.00
+ HCl
36.46
NaCl
58.44
+ H2O
18.02
+ +
Manufacturing Process Page 79
ToR Amendment Tagoor Chemicals Private Limited
Stage-9
NH
N
H3CCH2
O
1-Isopropenyl-1,3-dihydro-benzoimidazol-2-one
C10H10N2O174.2
+ Br Cl
1-Bromo-3-chloro-propane157.44
N
N
H3CCH2
O
Cl1-(3-Chloro-propyl)-3-isopropenyl-1,3-dihydro-benzoimidazol-2-one
C13H15ClN2O
250.72
+ NaBr
102.89
TBAB,WATER+ NaOH
40.00
+ H2O
18.02
Stage-10
N
N
H3CCH2
O
Cl
1-(3-Chloro-propyl)-3-isopropenyl-1,3-dihydro-benzoimidazol-2-one
C13H15ClN2O250.72
N
HN
O
Cl
1-(3-Chloro-propyl)-1,3-dihydro-benzoimidazol-2-one
C10H11ClN2O
210.66
+ Methanol HCl
36.5
H3CCH2
Cl2-Chloro-propene
C3H5Cl
76.52
+
Manufacturing Process Page 80
ToR Amendment Tagoor Chemicals Private Limited
Stage-11
NH
N
HNCl
O
5-Chloro-1-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one
C12H14ClN3O
251.71
+
1-(3-chloropropyl)-1,3-dihydro -2H-(Benzimidazole-2-one)
N
HN
O
Cl
C10H11ClN2O
210.66
+
+ NH4Cl
53.49
+
18.02
35.05
Ammonium chloride ,MIBK, Sodium hydroxide
& WaterNH4OH
H2ONHN
O
N
NHN
O
Cl
DomperidoneC22H24ClN5O2
425.91
Manufacturing Process Page 81
ToR Amendment Tagoor Chemicals Private Limited
Flow chart:
Methyl acrylate Mono methyl amine Methanol
Methanol lossOrganic residue
Stage -1Sodium methoxide Chloroform Water
Chloroform recovery Effluent water
Stage -2Ethylchloroformate Toluene
Toluene recovery
Stage -3Methanol Ammonia Sulphuric acid Raney Nickel Hydrogen
Generated water Methanol recovery
Stage -41,4-Dichloro-2-nitro-benzene (DCNB)Soda ash Water
Effluent water
Stage -5Methanol Raney nickel Hydrogen Toluene Water
Methanol recoveryToluene recovery
Stage-6Urea Ammonium hydroxide Hydrochloric acid Activated carbon Sodium hydroxideWater
Effluent water
Stage-1
Stage-2
Stage-3
Stage-4
Stage-5
Stage-6
Stage-7
Manufacturing Process Page 82
ToR Amendment Tagoor Chemicals Private Limited
Ortho phenylene diamine(OPDA)Methyl Aceto Acetate (MAA)Sodium hydroxide Hydrochloric acid (10%)O-XyleneWater
O -xylene recoveryeffluent waterStage-8
Stage-9
Stage-10
Stage-11
Stage-81-Bromo-3- chloro -propaneSodium hydroxideTBABWater
Effluent water
Stage-9Hydrochloric acid (12%)Methanol Water
Methanol RecoveryEffluent water
Stage -7Stage-10Methyl iso butyl ketoneAmmonium hydroxide (30%)Sodium hydroxide Ammonium chloride Water
Effluent water
Domperidone
Manufacturing Process Page 83
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of Domperidone Stage-1
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Methyl acrylate 411.00 Stage -1 483.00 Mono methyl amine 76.00 Methanol loss 100.00 Methanol 100.00 Organic residue 4.00 Total 587 Total 587
Material Balance of Domperidone Stage-2
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage -1 483.00 Stage -2 211.00 Sodium methoxide 169.00 Chloroform recovery 6745.00 Chloroform 7100.00 Chloroform loss 355.00 Water 4830.00 Effluent water
(Water-4787) 4787.00
By products (Sodium acetate -195, Methanol-250.98)
445.98
Process emission (Oxygen)
38.02
Total 12582 Total 12582
Material Balance of Domperidone Stage-3
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage -2 211.00 Stage -3 275.00 Ethylchloroformate 259.25 Toluene recovery 1074.00 Toluene 1130.00 Toluene loss 56.00 Process emission
(Chloromethane) 94.14
Organic residue 101.11 Total 1600.25 Total 1600.25
Manufacturing Process Page 84
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Domperidone Stage-4
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage -3 275.00 Stage -4 258.00 Methanol 250.00 Spent raney nickel
recovery 5.00
Ammonia 56.20 By product (Ammonia sulphate)
95.00
Sulphuric acid 70.20 Generated water 29.00 Raney Nickel 5.00 Methanol recovery 238.00 Hydrogen 4.00 Methanol loss 12.00 Organic residue 23.40 Total 660.4 Total 660.4
Material Balance of Domperidone Stage-5
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage -4 258.00 Stage -5 544.00 1,4-Dichloro-2-nitro-benzene (DCNB)
310.00 Effluent water (Water-2300 Soda ash -103.5)
2403.50
Soda ash 103.50 Process emission (Hydrogen Chloride)
24.00
Water 2300.00 Total 2971.5 Total 2971.5
Manufacturing Process Page 85
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Domperidone Stage-6
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage -5 544.00 Stage-6 389.00 Methanol 820.00 Methanol recovery 779.00 Raney nickel 5.00 Methanol loss 17.00 Hydrogen 4.00 Toluene recovery 494.00 Toluene 520.00 Toluene loss 10.00 Water 300.00 Effluent water
(Water-300, Toluene-16) 316.00
Raney nickel recovery 5.00 Process emission
(Oxygen) 53.11
Organic residue Process residue-105.89 Distillation Residue-24 (Methanol-24)
129.89
Total 2193 Total 2193
Material Balance of Domperidone Stage-7
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-6 389.00 Stage-7 550.00 Urea 138.00 Effluent water
(Water-2000, Generated Water-23.54 Sodium acetate-88.89)
2112.43
Ammonium hydroxide 444.00 By-product (Ammonium chloride- 565.50 )
565.50
Hydrochloric acid 306.00 Process emission (Ammonia-44.60, Carbon dioxide-57.47)
102.07
Activated carbon 35.00 Spent carbon 35.00 Sodium hydroxide 53.00 Water 2000.00 Total 3365 Total 3365
Manufacturing Process Page 86
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Domperidone Stage-8
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity in
Kg Ortho phenylene diamine(OPDA)
344.00 Stage-8 516.00
Methyl Aceto Acetate (MAA) 386.00 O –xylene recovery 2869.00 Sodium hydroxide 413.00 O –xylene loss 151.00 Hydrochloric acid (10%) 1270.00 Effluent water
(Water-5300, Generated Water-58, Water from hydrochloric acid -1143,excess sodium hydroxide-235, Sodium chloride-302)
7038.00
O-Xylene 3020.00 Process emission (Hydrogen-19.06, Carbon dioxide-139.94)
159.00
Water 5300.00 Total 10733 Total 10733
Material Balance of Domperidone Stage-9
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-8 516.00 Stage-9 608.00 1-Bromo-3- chloro -propane 471.00 Effluent water
(Water-3440 , Generated Water-54, TBAB-42)
3536.00
Sodium hydroxide 291.00 By-product (Sodium bromide )
604.00
TBAB 42.00 Organic residue 12.00 Water 3440.00 Total 4760 Total 4760
Manufacturing Process Page 87
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Domperidone Stage-10
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-9 608.00 Stage-10 462.00 Hydrochloric acid (12%) 730.00 Methanol Recovery 475.00 Methanol 500.00 Methanol loss 25.00 Water 2645.00 Effluent water
(Water-2645,2-chloro propene- 186, water from Hydrochloric acid-642 )
3473.00
Organic residue 48.00 Total 4483 Total 4483
Material Balance of Domperidone Stage-11
Batch Size: 840Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage -7 550.00 Domperidone 840.00 Stage-10 462.00 Effluent water
(Water-5000, Methyl iso butyl ketone-200, Sodium hydroxide-2000, Generated water-40, Water from Ammonium hydroxide 420)
7660.00
Methyl iso butyl ketone 200.00 By product (Ammonium chloride-1017)
1017.00
Ammonium hydroxide (30%) 600.00 Organic residue 195.00 Sodium hydroxide 2000.00 Ammonium chloride 900.00 Water 5000.00 Total 9712 Total 9712
Manufacturing Process Page 88
ToR Amendment Tagoor Chemicals Private Limited
DONEPEZIL HYDROCHLORIDE
Process Description:
Stage-1:
5,6 Dimethoxy-2-(Piperidin-4-yl) methyl)Indan-1-one reacts with Chloromethyl
Benzene in presence of Sodium bicarbonate , Iso propyl alcohol, Tetra butyl
ammonium bromide,Toluene, Methanol, IPA-HCl, Sodium hydroxide (NaOH),Con
HCl, Carbon and Water to give Stage–1 product
Stage-2:
Stage-1 product undergoes purification with Methylene dichloride, Acetone and
Carbon to give Donepezil HCl.
Route of Synthesis
Stage-1:
5,6-dimethoxy-2-(piperidin-4-yl-methyl)indan-1-one
O
O
NH
O
Cl
(chloromethyl)benzene
O
O
N
O
+
Methanol
TBAB/Toluene
C17H23NO3
289.37
C7H7Cl126.58
C24H29NO3
379.49
2-(1-Benzyl-piperidin-4-ylmethyl)-5,6-dimethoxy-indan-1-one
+ HCl
36.46
Manufacturing Process Page 89
ToR Amendment Tagoor Chemicals Private Limited
Stage-2:
O
O
N
O
C24H29NO3
379.49
2-(1-Benzyl-piperidin-4-ylmethyl)-5,6-dimethoxy-indan-1-one
+ HCl
36.46
O
O
N
O
HCl
C24H30ClNO3
415.95
MDC/Acetone
DONEPEZIL HCl
Flow Chart
Stage-1
Stage-2
DONEPEZIL HYDROCHLORIDE
5,6 Dimethoxy-2-(Piperidin-4-yl) methyl)Indan-1-one Chloromethyl BenzeneActivated CarbonSodium hydroxideTBABTolueneIsopropyl alcoholMethanol
Toluene RecoveryMethanol RecoveryIsopropyl alcohol RecoveryEffluent water
MDC RecoveryAcetone Recovery
Stage-1Activated CarbonMethylene DichlorideAcetoneHydrochloric Acid
Manufacturing Process Page 90
ToR Amendment Tagoor Chemicals Private Limited
Material Balance
Material Balance of Donepezil Hydrochloride Stage-1
BatchSize:100.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 5,6 Dimethoxy-2-(Piperidin-4-yl) methyl)Indan-1-one
87.00 Stage-1 102.00
Chloromethyl Benzene 38.00 Toluene Recovery 285.00 Activated Carbon 10.00 Toluene Loss 10.00 Sodium hydroxide 15.00 Isopropyl alcohol Recovery 333.00 TBAB 2.00 Isopropyl alcohol Loss 18.00 Toluene 300.00 Methanol Recovery 190.00 Isopropyl alcohol 350.00 Methanol Loss 5.00 Methanol 200.00 Effluent Water 505.00 Water 500.00 (Water-500,Toluene-3,TBAB-2) 0.00 Process emission 10.88 (Hydrogen Chloride-10.88) 0 Spent Carbon 10.00 Organic Residue 33.12 (Process residue-17.12,
Distillation residue -16 (Toluene-2, Isopropyl alcohol-9,Methanol-5)
Total 1502.00 Total 1502.00
Material Balance of Donepezil Hydrochloride Stage-2
BatchSize:100.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 102.00 Donepezil Hydrochloride 100.00 Activated Carbon 10.00 Methylene Dichloride Recovery 760.00 Methylene Dichloride 800.00 Methylene Dichloride Loss 16.00 Acetone 300.00 Acetone Recovery 285.00 Hydrochloric Acid 9.72 Acetone Loss 10.00 Spent Carbon 10.00 Organic Residue 40.72 Process residue-11.72
Distillation residue-29 (Acetone-5,MDC-24)
Total 1221.72 Total 1221.72
Manufacturing Process Page 91
ToR Amendment Tagoor Chemicals Private Limited
EBASTINE
Process Description:
Stage-1:
4-Benzhydryloxy-piperidine-1-carboxylic acid ethyl ester undergoes Hydrolysis with
Potassium Hydroxide in presence of IPA, Hydrochloric acid and Acetone to give
Stage-1 product.
Stage-2: Stage-1 Product undergoes salt formation with Hydrochloric acid in presence of
Toluene to give Stage-2 product.
Stage-3: Tert-Butyl-benzene reacts with 4-Chloro-Butyryl Chloride in presence of
Dichloromethane ,Aluminium chloride, Ice water and water to give stage-3 Product.
Stage-4:
Stage-3 Product reacts with stage-1 product in presence of Methanol, Toluene and
TBAB to give stage-4 Product.
Stage-5:
Stage-4 Product undergoes Purification in presence of Carbon to give Ebastine.
Manufacturing Process Page 92
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
O
N O
O
CH3
4-Benzhydryloxy-piperidine-1-carboxylic acid ethyl ester
C21H25NO3
339.43
+
KCl
74.55
+ 0.5 O2
16.00
KOH
56.11
+ HCl
36.46
Ethyl formate
O O +
C3H6O2
74.08
O
NH
4-Benzhydryloxy-piperidine
C18H21NO
267.37
+
Chloroform, Isopropylalcohol& Acetone
Manufacturing Process Page 93
ToR Amendment Tagoor Chemicals Private Limited
Stage-2:
+ HCl
36.46
O
NH
4-Benzhydryloxy-piperidine
C18H21NO
267.37
O
NH
. HCl
303.83
C18H22ClNO
4-Benzhydryloxy-piperidine Hydrochloride
Stage-3
CH3H3C
CH3
tert-Butyl-benzene
C10H14
134.22
+
ClCl
O
4-Chloro-butyryl chlorideC4H6Cl2O
141.0
Dichloromethane, n-Hexane, Ice water & DM water
CH3
H3C
CH3
O
Cl
1-(4-tert-Butyl-phenyl)-4-chloro-butan-1-one
C14H19ClO
238.75
+ 4 HCl
+ AlCl3
133.34
+ Al(OH)3
78.00
+ 3 H2O
54.05
145.84
Manufacturing Process Page 94
ToR Amendment Tagoor Chemicals Private Limited
Stage-4:
CH3
H3C
CH3
O
Cl
1-(4-tert-Butyl-phenyl)-4-chloro-butan-1-one
C14H19ClO
238.75
O
NH
4-Benzhydryloxy-piperidine
C18H21NO
267.37
+ + 0.5 K2CO3
69.10
Methanol, Toluene ,TBAB, Potassium iodide
O N
O
CH3
CH3
CH3
4-(4-Benzhydryloxy-piperidin-1-yl)-1-(4-tert-butyl-phenyl)-butan-1-one
C32H39NO2
469.66
+ KCl
74.55+ 0.5 CO2
22.00
+ 0.5 H2O
9.01
Manufacturing Process Page 95
ToR Amendment Tagoor Chemicals Private Limited
Stage-5:
O N
O
CH3
CH3
CH3
4-(4-Benzhydryloxy-piperidin-1-yl)-1-(4-tert-butyl-phenyl)-butan-1-one
C32H39NO2
469.66O N
O
CH3
CH3
CH3
EbastineC32H39NO2
469.66
Methanol
Activated Carbon
Manufacturing Process Page 96
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
Stage-2
4-Benzhydryloxy-piperidine-1-carboxylic acid ethyl esterPotassium HydroxideHydrochloric acidChloroform IPAAcetone
IPA RecoveryAcetone RecoveryEffluent water
Stage-1Hydrochloric acidToluene
Toluene RecoveryEffluent water
Stage-3
Stage-4
Stage-24-Chloro-butyryl chlorideAluminum chlorideDichlorormethanen-Hexane
n-Hexane RecoveryDichloromethane RecoveryEffluent water
Stage-34-Benzyhydroloxy-piperidnePotassium carbonateMethanolTolueneTBABPotassium Iodide
Toluene RecoveryMethanol RecoveryEffluent water
Stage-5
Stage-4Methanol Activated carbonIPA
IPA Recovery
EBASTINE
Manufacturing Process Page 97
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of Ebastine Stage-1
Batch Size: 500.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 4-Benzhydryloxy-piperidine-1-carboxylic acid ethyl ester 420.00 Stage-1 314.00
Potassium Hydroxide 70.00 Acetone Recovery 385.00 Hydrochloric acid 45.00 Acetone Loss 10.0 Chloroform 400.00 Chloroform Recovery 385.00 IPA 400.00 Chloroform Loss 10.00 Acetone 400.00 IPA Recovery 385.00 Water 400.00 IPA Loss 10.00 Effluent water 492.00 (Water-400, Ethyl formate-92) 0 By product
(Potassium chloride-92.24,) 92.24
Process emission 20.00 (Oxygen-20) 0 Organic residue 31.76 Process residue –16.76
Distillation residue-15 (Acetone-5,Chloroform-5,IPA-5)
Total 2135.00 Total 2135.00
Material Balance of Ebastine Stage-2
Batch Size: 500.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 314.00 Stage-2 340.00 Hydrochloric acid 43.00 Toluene Recovery 385.00 Toluene 400.00 Toluene Loss 10.0 Water 400.00 Effluent water 403.00 (Water-400,Toluene-3) 0 Organic residue 19.00 Process residue –17
Distillation residue-2 (Toluene-2)
Total 1157.00 Total 1157.00
Manufacturing Process Page 98
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Ebastine Stage-3
Batch Size: 500.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 165.00 Stage-3 280.00 4-Chloro-butyryl chloride 173.00 n-Hexane Recovery 385.00 Aluminum chloride 164.00 n-Hexane Loss 10.0 Dichlorormethane 400.00 Dichloromethane Recovery 385.00 n-Hexane 400.00 Dichloromethane Loss 10.00 Water 800.00 By product
(Aluminum chloride solution (12% )
800.00
Process emission 179.00 (Hydrogenchloride-179) 0 Organic residue 53.00 Process residue –43
Distillation residue-10 (n-Hexane-5,Dichloromethane-5)
Total 2102 Total 2073
Material Balance of Ebastine Stage-4
Batch Size: 500.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 280.00 Stage-4 525.00 4-Benzyhydroloxy-piperidne 314.00 Toluene Recovery 385.00 Potassium carbonate 81.00 Toluene Loss 10.00 Methanol 400.00 Methanol Recovery 385.00 Toluene 400.00 Methanol Loss 10.00 TBAB 5.00 Effluent water 428.56 Potassium Iodide 10.00 (Water-400,Generated water-
10.56, ,Toluene-3,TBAB-5,Potassium Iodide-10)
0
Water 400.00 Process emission (Carbon dioxide-26)
26.00
By product (Potassium Chloride-87.43)
87.43
Organic residue Process residue –26.01 Distillation residue-7 (Methanol-5,Toluene-2)
33.01
Total 1890 Total 1890
Manufacturing Process Page 99
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Ebastine Stage-5
Batch Size: 500.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-4 525.00 Ebastine 500.00 Methanol 400.00 Methanol Recovery 385.00 Activated carbon 5.00 Methanol Loss 10.00 IPA 400.00 IPA Recovery 385.00 IPA Loss 10.00 Spent carbon 5.00 Organic residue 35.00 Process residue –25
Distillation residue-10 (Methanol-5,IPA-5)
Total 1330.00 Total 1330.00
ESOMEPRAZOLE MAGNESIUM TRIHYDRATE
Process Description:
Stage-1
Omeprazole sulfide reacts with cumin hydro peroxide and magnesium chloride hexa
hydrate in the presence of Toluene to give Esomeprazole Magnesium
Manufacturing Process Page 100
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1:
N
OCH3H3C CH3
CH2
SNH
N OCH3
5-Methoxy-2-[(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl Thio]-1H -Benzoimidazole
C17H19N3O2S2X329.41=658.82
+
H3C OCH3
Cumin hydroperoxide
OH
C9H12O22X152.19=304.38
+ MgCl2. 6H2O
Magnesium chloride Hexahydrate
203.00
Toluene
+OHH3C
CH3
C9H12O
2X136.19=272.38
Cumin hydroxide
2
N
OCH3H3C CH3
CH2
SN
N OCH3O
2
Mg 3H2O
Esomeprazole Magnesium Tri Hydrate
C17H18N3O3S.Mg3H2O
767.15
2 + 2HCl
72.92
+ 3H2O
54.00
Flow Chart:
Stage-1
Omeprazole sulphideToluene D(-)-Diethyl tartrateN,N-DiisopropylethylamineMethanol
Methanol Rec
ESOMEPRAZOLE MAGNESIUM TRIHYDRATE
Manufacturing Process Page 101
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material balance of Esomeprazole Magnesium Trihydrate Stage-1
Batch Size: 100.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
In Kg
Omeprazole sulphide 90.00 Esomeprazole Magnesium Tri hydrate
100.00
Toluene 400.00 Toluene Recovery 385.00 D(-)-Diethyl tartrate 12.00 Toluene Loss 15.00 Titanium tetra iso propoxide 7.50 Methanol Recovery 285.00 N,N-Di isopropyl ethylamine 5.00 Methanol Loss 15.00 Cumin hydro peroxide 42.00 Dichloromethane Recovery 385.00 Potassium hydroxide 44.00 Dichloromethane Loss 15.00 Methanol 300.00 Ethyl acetate Recovery 385.00 Dichloromethane 400.00 Ethyl acetate Loss 15.00 Acetic acid 15.00 Effluent water 1335.87 Sodium sulfate 10.00 (Water-1200,Generated water-
7.29,Potassium hydroxide-44, Acetic acid-15,Titanium tetra isopropoxide-7.5,N,N-Diisopropylethylamine-5,D(-) Diethyl tartarate-12,Cumin hydroxide-37.17,Hydrochloric acid-7.91)
0
MgCl2 6H2O 27.75 Inorganic Residue 10.00 Ethyl acetate 400.00 (Sodium sulphate-10) water 1200.00 Organic Residue 7.38 Process residue-7.38 Total 2953.25 Total 2953.25
Manufacturing Process Page 102
ToR Amendment Tagoor Chemicals Private Limited
ESOMEPRAZOLE SODIUM.
Process Description
Stage-1
5-Methoxy-2-[(4-Methoxy-3,5-Dimethyl-2-pyridinyl)MethylThio]-1H-Benzimidazole
reacts with Cumin hydro peroxide and Potassium hydroxide in the presence of
Toluene to give stage-1 product.
Stage-2
Stage-1 reacts with acetic acid and sodium hydroxide in the presence of MDC to
give Esomeprazole Sodium.
. Route of synthesis:
Stage-1:
N
OCH3
H3C CH3
CH2
SNH
N OCH3
N
OCH3
H3C CH3
CH2
SN
N
5-Methoxy-2-[(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl Thio]-1H -Benzoimidazole
C17H19N3O2S
329.41
+
H3C O
CH3
Cumin hydroperoxide
OH
C9H12O2
152.19
+ KOH
Potassium hydroxide
56.10
Toluene
OCH3
K+
O
H2O +
OHH3C
CH3
C9H12O
136.19
Cumin hydroxide
C17H20KN3O4S
401.52
Esomeprazole potassium salt.Monohydrate
Manufacturing Process Page 103
ToR Amendment Tagoor Chemicals Private Limited
Stage-2:
N
OCH3
H3C CH3
CH2
SN
N OCH3
K+
O
H2O
C17H20KN3O4S
401.52
Esomeprazole potassium salt.Monohydrate
+
Acetic acid
60.05
+ NaOH
Sodium hydroxide
N
OCH3
H3C CH3
CH2
S
N
N OCH3O
H2O + CH3COOK
98.14
Potassium acetateEsomeprazole Sodium
385.41
H3C
O
OH
40.00
Na
C17H18N3NaO3S.H2O
+ H2O
18.00
MDC
Flowchart:
Stage-1
5-Methoxy-2-[(4-Methoxy-3,5-Dimethyl-2-pyridinyl)Methyl Thio]-1H-Benzimidazole Cumin hydroperoxide Potassium hydroxide Toluene
Toluene RecoveryCumin hydroxide
Stage-2
Stage-1Acetic acidMDCSodium hydroxide
MDC RecoveryPotassium acetate
ESOMEPRAZOLE SODIUM
Manufacturing Process Page 104
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance Of Esomeprazole sodium Stage-1
Batch Size: 100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Omeprazole sulfide 96.00 Stage-1 110.00 Cumin Hydroperoxide 44.35 Toluene Recovery 285.00 Potassium hydroxide 16.35 Toluene Loss 10.00 DET 11.30 Methanol Recovery 95.00 Ti(IV)Isopropoxide 2.50 Methanol Loss 3.00 NEDIPA 4.50 NEDIPA Loss 4.50 Toluene 300.00 Organic Residue 67.50 Methanol 100.00 Process residue-60.50
Organic impurities-7.06( Ti(IV)Isopropoxide-2.5, Cumin hydroxide-39.64,DET-11.3) Distillation residue-7 (Toluene-5,Methanol-2)
Total 575.00 Total 575.00
Material Balance Of Esomeprazole sodium Stage-2
Batch Size: 100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage -1 110.00 Esomeprazole Sodium 100.00 Acetic acid 16.40 MDC Recovery 285.00 Sodium hydroxide 10.90 MDC Loss 10.00 MDC 300.00 Ethyl acetate Recovery 143.00 Ethyl acetate 150.00 Ethyl acetate Loss 2.00 Activated carbon 5.00 Effluent water 834.68 Water 800.00 (Water-800,Generated water
-4.84,Potassium acetate-26.84,Ethyl acetate-3)
0
Spent carbon 5.00 Organic residue 12.62 Process residue-5.62
Distillation residue-7 MDC-5,Ethyl acetate -2)
Total 1392.30 Total 1392.30
Manufacturing Process Page 105
ToR Amendment Tagoor Chemicals Private Limited
FEXOFENADINE HYDROCHLORIDE
Process Description:
Stage-1
2-[4-(4-Chloro-butyryl)-cyclohexyl]-2-methyl-propionic acid methyl ester on
undergoes condensation with Azacyclonol in presence of Sodium bicarbonate and
MIBK to give stage-1 product.
Stage-2
Stage-1 product undergoes reduction with, Sodiumborohydride and water in
presence of Methanol to give stage-2 product.
Stage-3
Stage-2 product undergoes salt formation with HCl in presence of IPA to give
Fexofenadine Hydrochloride
Manufacturing Process Page 106
ToR Amendment Tagoor Chemicals Private Limited
FEXOFENADINE HYDROCHLORIDE
Route of Synthesis:
Stage-1
+ + NaHCO3
84.01
H3C
CH3
COOCH3
Cl
O
2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid methyl ester
HN
OH
Azacyclonol
H3C
CH3
COOCH3
ON
OH
MIBK
+ NaCl + CO2 + H2O
58.44 44.0 18.02
C15H19ClO3
282.10
C18H21NO
267.37
2-(4-{4-[4-(Hydroxy-diphenyl-methyl)-piperidin-1-yl]-butyryl}-phenyl)-2-methyl-
propionic acid methyl esterC33H39NO4
513.67
Manufacturing Process Page 107
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
H3C
CH3
COOCH3
ON
OH
H3C
CH3
COOH
OHN
OH
+ NaBH4
37.83
+ 4 H2O
72.06
Methanol
+ H3BO3
61.83
+ CH3ONa
54.02
+
2-(4-{4-[4-(Hydroxy-diphenyl-methyl)-piperidin-1-yl]-butyryl}-phenyl)-2-methyl-propionic acid methyl ester
C33H39NO4
513.67
FexofenadineC32H39NO4
501.66
3 H2
6.00
Manufacturing Process Page 108
ToR Amendment Tagoor Chemicals Private Limited
Stage-3
H3C
CH3
COOH
OHN
OH + HClIPA
H3C
CH3
COOH
OHN
OH HCl
Fexofenadine hydrochloride
C32H40ClNO4
538.12
FexofenadineC32H39NO4
501.66
36.46
FEXOFENADINE HYDROCHLORIDE
Flow Chart:
Dimethyl phenyl acetateSodium BicarbonateAzacyclonolMethyl isobutyl ketoneEthyl Acetate
Stage-1 Ethyl acetate Rec
Stage-2 Methanol Rec
Stage-1Sodium BorohydrideSodium HydroxideAcetic AcidMethanol
Stage-3 IPA RecStage-2Hydrochloric acidIsopropyl alcohol
FEXOFENADINE HYDROCHLORIDE
Manufacturing Process Page 109
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of Fexofenadine Hydrochloride Stage-2
Batch Size: 200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 227.00 Stage-2 203.00 Sodium Borohydride 16.50 Methanol recovery 760.00 Activated carbon 10.00 Methanol Loss 16.00 Methanol 800.00 Effluent Water 519.30 Water 500.00 (Water-468.22, Boric acid-27.24,
Sodium methoxide-23.84) 0
Spent Carbon 10.00 Process Emissions 2.49 (Hydrogen-2.49) 0 Organic Residue 42.71 Process Residue-22.71
Organic Impurities-12.31 (Sodium methoxide-10.4) Distillation Residue-24 (Methanol-24)
Total 1553.50 Total 1553.50
Material Balance of Fexofenadine Hydrochloride Stage-1
Batch Size: 200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 2-[4-(4-Chloro-butyryl)-cyclohexyl]-2-methyl-propionic acid methyl ester
136.00 Stage-1 227.00
Sodium Bicarbonate 40.40 Ethyl Acetate recovery 665.00 Azacyclonol 129.00 Ethyl Acetate Loss 14.00 Methyl isobutyl ketone 200.00 Methyl Isobutyl Ketone Recovery 190.00 Ethyl Acetate 700.00 Methyl Isobutyl Ketone Loss 8.00 Water 600.00 Effluent water 641.71 (Water-600,Generated water-
8.56,Sodium chloride-28.15, Ethyl acetate-5)
Process Emission 21.08 (Carbon dioxide -21.08) Organic Residue 38.61 (Process Residue-20.61,
Distillation Residue-18, (Ethyl acetate-16,MIBK-2)
Total 1805.40 Total 1805.40
Manufacturing Process Page 110
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Fexofenadine Hydrochloride Stage-3
Batch Size: 200Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 203.00 Fexofenadine Hydrochloride 200.00 Hydrochloric acid 14.50 Isopropyl Alcohol Recovery 760.00 Isopropyl alcohol 800.00 Isopropyl Alcohol Loss 16.00 Organic Residue 41.50 Process Residue-17.50
Distillation Residue-24 (IPA-24)
Total 1017.50 Total 1017.50
HALOPERIDOL
Process description:
Stage-1:
1-4-Fluoro Phenyl-pentan-1-one reacts with 4-(Chloro phenyl)piperidine 4-ol in
presence of Potassiumcarbonate, Toluene , Cholofrom, Potassium Iodide &Water to
give Stage-1 Product
Stage-2:
Stage-1 Product undergoes purification in Methanol & activated carbon to give of
Haloperidol.
Manufacturing Process Page 111
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
F
O
1-(4-Fluoro-phenyl)-pentan-1-one
C11H13FO180.22
+ NH
HO
Cl
4-(4-Chloro-phenyl)-piperidin-4-ol
C11H14ClNO211.69
Toluene,Chloroform,
Haloperidol(Crude)
C21H23ClFNO2
375.86
+ H2O
+ CH3OH
32.04
18.02
+
2.02
+K2CO3 2 HCl
138.21 72.92
+
Activated carbon,Potassium iodide,
2 KCl
149.10
H2CO3
62.02
+ H2+F
NO
OH
Cl
Stage-2
Haloperidol(Crude)
C21H23ClFNO2
375.86
F
NO
OH
Cl
Activated carbon,Methanol
Haloperidol(Pure)
C21H23ClFNO2375.86
F
NO
OH
Cl
Manufacturing Process Page 112
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
Haloperidol
Stage-2
1-4-Fluoro Phenyl-pentan-1-one4-(Chloro phenyl)piperidine 4-olPotassium carbonatePotassium IodideHydrochloric acidTolueneChloroform
Toluene RecoveryChlorofrom recoveryEffluent water
Stage-1Spent CarbonMethanol
Methanol RecoverySpent carbon Recovery
Material Balance:
Material Balance of Haloperidol Stage-1
Batch Size: 100 Kg Name of the input Quantity
in Kg Name of the out put Quantity in
Kg 1-4-Fluoro Phenyl-pentan-1-one
57.00 Stage-I 110.00
4-(Chloro phenyl)piperidine 4-ol 67.00 Mixed solvent (Toluene Recovery + Generated Methanol )
390.08
Potassium carbonate 44.00 Toluene loss 8.00 Potassium Iodide 2.00 Chloroform Recovery 285.00 Hydrochloric acid 23.00 Chloroform loss 15.00 Toluene 400.00 Effluent water 567.10 Chloroform 300.00 (water -494.36, Potassium
Chloride-47.14, Carbonic acid-19.60, Toluene-6)
0
Water 500.00 Process emission 0.62 (Hydrogen-0.62) 0 Organic residue 17.20 Process residue-11.20
Distillation residue-6 (Toluene-6)
Total 1393.00 Total 1393.00
Manufacturing Process Page 113
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Haloperidol Stage-2
Batch Size: 100 Kg Name of the input Quantity
in Kg Name of the out put Quantity in
Kg Stage-1 110.00 Haloperidol 100.00 Spent Carbon 4.00 Methanol Recovery 570.00 Methanol 600.00 Methanol Loss 12.00 Spent carbon Recovery 4.00 Organic residue 28.00 Process residue- 10
Distillation residue-18 (Methanol-18)
Total 714.00 Total 714.00
ITOPRIDE HYDROCHLORIDE
Process Description
Stage-1
4-Hydroxy benzaldehyde reacts with (2-Chloroethyl)-dimethylamine hydrochloride
and Triethyl amine in presence of Chloroform to give stage-1 product.
Stage-2
Stage-1 product reacts with Hydroxyl amine sulfate and Hydrogen gas in presence of
Raney Nickel in presence of Methanol to give Stage-2 product.
Stage-3
Stage-2 product undergoes condensation with 3, 4-Dimethoxy benzoyl chloride in
presence of Toluene to give stage-3 product.
Stage-4
Stage-3 product undergoes purification in presence of Methanol and Isopropyl
alcohol to give Itopride Hydrochloride.
Manufacturing Process Page 114
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis
Stage-1:
H
OHO
4-Hydroxy-benzaldehyde
C7H6O2
122.12
+
NH3C
CH3
Cl
(2-Chloro-ethyl)-dimethyl-amine Hydrochoride
HCl
C4H11Cl2N
144.04
+
Triethyl-amine
Chloroform
202.00
H
O
O
NH3C
CH3
4-(2-Dimethylamino-ethoxy)-benzaldehyde
C11H15NO2
193.24
+
Triethyl amine Hydrochloride
275.30
N
N HCl.
2
2
C6H15N
C6H16ClN
Stage-2:
H
O
O
NH3C
CH3
4-(2-Dimethylamino-ethoxy)-benzaldehyde
C11H15NO2
193.24
+ (NH2OH)H2SO4 +Raney Ni
Methanol
NH2
O
NH3C
CH3
[2-(4-Aminomethyl-phenoxy)-ethyl]-dimethyl-amine
C11H18N2O
194.27
+ H2SO4
Sulfuric acid
98.00
4.00
+
36.00
131.11
2 H2
2 H2O
Hydroxyl amine sulphate
Manufacturing Process Page 115
ToR Amendment Tagoor Chemicals Private Limited
Stage-3:
NH2
O
NH3C
CH3
[2-(4-Aminomethyl-phenoxy)-ethyl]-dimethyl-amine
C11H18N2O
194.27
+
Cl
O
H3CO
OCH3
3,4-Dimethoxy-benzoyl chloride
C9H9ClO3
200.62
Toluene
HN
ON
CH3
H3C O
OCH3
OCH3
HCl
C20H27ClN2O4
394.89
Itopride Hydrochloride (Crude)
Stage-4:
HNON
CH3
H3C O
OCH3
OCH3
HCl
C20H27ClN2O4
394.89
Itopride Hydrochloride (Crude)
Methanol HNON
CH3
H3C O
OCH3
OCH3
HCl
C20H27ClN2O4
394.89
Itopride Hydrochloride
Manufacturing Process Page 116
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart:
4-Hydroxy benzaldehyde (2-Chloroethyl)-dimethylamine hydrochlorideTriethyl amine Chloroform
Chloroform Rec
Stage-1 Hydroxyl amine sulfate Raney Ni Methanol
Methanol Rec
Stage-2 3, 4-Dimethoxy benzoyl chlorideToluene
Toluene Rec
Stage-3 MethanolIsopropyl alcohol
Methanol RecIPA Rec
ITOPRIDE HYDROCHLORIDE
Stage-1
Stage-2
Stage-3
Stage-4
Material Balance:
Material Balance of Itopride Hydrochloride Stage-1
Batch Size: 100.0Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 4-Hydroxy benzaldehyde 37.00 Stage-1 56.00 (2-Chloro ethyl)-dimethyl hydrochloride 43.60 Chloroform Recovery 475.00
Triethylamine 61.20 Chloroform Loss 25.00 Chloroform 500.00 Effluent water 383.40
Water 300.00 (Water-300, Triethyl amine HCl-83.40)
0
Organic residue 2.40 Process residue-2.4 Total 941.80 Total 941.80
Material Balance of Itopride Hydrochloride
Manufacturing Process Page 117
ToR Amendment Tagoor Chemicals Private Limited
Stage-2 Batch Size: 100.0Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-1 56.00 Stage-2 54.00 Hydroxyl amine sulphate 38.00 Methanol Recovery 570.00 Methanol 600.00 Methanol Loss 12.00 Raney nickel 5.00 Effluent water 338.0
Hydrogen gas 1.12 (Water-300,Generated water-10.41,Sulfuric acid-28.39)
0
Water 300.00 Spent Raney Nickel Recovered 5.00 Organic residue 21.12
Process residue-3.12
Distillation residue-18 (Methanol-18)
Total 1000.12 Total 1000.12
Material Balance of Itopride Hydrochloride Stage-3
Batch Size: 100.0Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 54.00 Stage-3 105.00 3,4-Dimethoxy benzoyl chloride 55.50 Toluene Recovery 380.00 Toluene 400.00 Toluene Loss 12.00 Water 200.00 Effluent water 204.00 (Water-200,Toluene-4) 0 Organic Residue 8.50
Process residue-4.50
Distillation residue-4 (Toluene-4)
Total 709.50 Total 709.50
Manufacturing Process Page 118
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Itopride Hydrochloride Stage-4
Batch Size: 100.0Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 105.00 Itopride Hydrochloride 100.00 Methanol 500.00 Methanol Recovery 475.00 Isopropyl alcohol 500.00 Methanol Loss 10.00 Activated carbon 3.50 Isopropyl alcohol Recovery 475.00 Water 200.00 Isopropyl alcohol Loss 10.00 Effluent water 200.00 (Water-200) 0 Spent carbon 3.50 Organic residue 35.00
Process residue-5 Distillation residue-30 (Methanol-15, Isopropyl alcohol-15)
Total 1308.5 Total 1308.50
ITRACONAZOLE
Process Description:
Stage-1
1-(4-Methoxy-Phenyl)-piperazine reacts with 1-Bromo-4-nitro-benzene in presence of MDC and Methanol to give Stage-1 Product.
Stage-2:
Stage-1 Product reacts with Hydrogen in presence of Pd/c catalyst and DMF to give Stage-2 Product.
Stage-3:
Stage-2 product reacts with Phenyl Chloro formate in presence of Sodium bicarbonate and MDC to give Stage-3 product.
Stage-4:
Stage-3 product reacts with Hydrazine hydrate in presence of 1,4-Dioxane to give Stage-4 product.
Stage-5:
Stage-4 Product reacts with Formamidine in presence of Acetic acid and acetone to give Stage-5 product.
Manufacturing Process Page 119
ToR Amendment Tagoor Chemicals Private Limited
Stage-6:
Stage-5 product reacts with 2-Bromo-Butane in presence of Potassium carbonate and Methanol to give Stage-6 product.
Stage-7:
Stage-6 product reacts with Hydrobromic acid in presence of Sodium carbonate nd Methanol to give stage-7 Product.
Stage-8:
Step-A:
2,4Dichloroacetopheneone reacts with Glycerol and Bromine in presence of Toluene, PTSA and n-Butanol to give Step-A product.
Step-B:
Step-A product reacts with Benzyl Chloride in presence of Toluene and Methanol to give Stage-8 Product.
Stage-9:
Stage-8 Product reacts with 1,2,4-Triazole in presence of Potassium Carbonate , Sodium Hydroxide ,DMF and water to giveStage-9 Product.
Stage-10:
Stage-9 Product reacts with Methanol Sulfanyl Chloride in presence of TEA, MDC and water to give Stage-10 product.
Stage-11:
Stage-10 Product undergoes condensation with Stage-7 Product in presence of potassium hydroxide and Methanol to give Itraconazole.
Manufacturing Process Page 120
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis
Stage-1:
HN N OCH3
C11H16N2O
1-(4-Methoxy-phenyl)-piperazine
192.26
+ BrO2N
1-Bromo-4-nitro-benzeneC6H4BrNO2
202.01
NO2N N OCH3
1-(4-Methoxy-phenyl)-4-(4-nitro-phenyl)-piperazineC17H17N3O3
313.35
+ HBr
80.91
MDC
Methanol
Stage-2:
H3CO N N NO2
C17H19N3O3
313.35
+ 3H2 pd/Catalyst
H3CO N N NH2
C17H21N3O283.37
+ 2H2O
36.04
Hydrogen
6.05
DMF1-(4-Methoxy-phenyl)-4-(4-nitro-phenyl)-
piperazine
4-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-phenylamine
Manufacturing Process Page 121
ToR Amendment Tagoor Chemicals Private Limited
Stage-3:
H3CO N N NH2
C17H21N3O
283.37
+OCl
O+ NaHCO3
Phenyl chloro formate
C7H5ClO2
156.57
84.01
H3CO N N NHCOOPh
C24H25N3O3
403.47
+ NaCl + CO2 + H2O
58.44 44.01 18.02
4-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-phenylamine
{4-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-phenyl}-carbamic acid phenyl ester
MDC
Stage-4:
H3CO N N NHCOOPh
C24H25N3O3
403.47
+ N2H4.H2O
Hydrazine hydrate
50.06
1,4-Dioxane
H3CO N N NHCONHNH2
C18H23N5O2
341.41
+
OH
PhenolC6H6O
94.11
+ H2O
18.02
{4-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-phenyl}-carbamic acid phenyl ester
1,3-Dimethyl-7-{2-[(1-phenyl-2-propanyl)amino]ethyl}-3,7-dihydro-1H-purine-2,6-dione
Manufacturing Process Page 122
ToR Amendment Tagoor Chemicals Private Limited
Stage-5:
H3CO N N NHCONHNH2
C18H23N5O2
341.41
+ H2N NH + 2CH3COOH
FormamidineCH4N2
44.07
120.10
H3CO N N NN
NH
O
C19H21N5O2351.40
+
Ammonium acetate
2CH3COONH4
154.16
1,3-Dimethyl-7-{2-[(1-phenyl-2-propanyl)amino]ethyl}-3,7-dihydro-1H-purine-2,6-dione
2-{4-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-phenyl}-2,4-dihydro-[1,2,4]triazol-3-one
Stage-6:
H3CO N N NN
NH
O
C19H21N5O2
351.40
+ +
C4H9Br
137.02
69.10
Methanol
C23H29N5O2
407.51
+ KBr + 1/2CO2 + 1/2 H2O
119.0 22.0 9.01
2-{4-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-phenyl}-2,4-dihydro-[1,2,4]triazol-3-one
H3CCH3
Br
2-Bromo-butane
1/2 K2CO3
H3CO N N NN
N
O
CH3
CH3
4-Isobutyl-2-{4-[4-(4-methoxy-phenyl)-piperazin-1-yl]-phenyl}-2,4-dihydro-[1,2,4]triazol-3-one
Manufacturing Process Page 123
ToR Amendment Tagoor Chemicals Private Limited
Stage-7:
H3CO N N NN
N
O
CH3
CH3
C23H29N5O2
407.51
+ 2HBr + Na2CO3
Hydrobromic acid161.82
106.0
+ CH3OH + 2NaBr +
Methanol
C22H27N5O2
393.48
32.04 205.79 44.01
4-Isobutyl-2-{4-[4-(4-methoxy-phenyl)-piperazin-1-yl]-phenyl}-2,4-dihydro-[1,2,4]triazol-3-one
HO N N NN
N
O
CH3
CH3
2-{4-[4-(4-Hydroxy-phenyl)-piperazin-1-yl]-phenyl}-4-isobutyl-2,4-dihydro-[1,2,4]triazol-3-one
CO2
Stage-8:
Step-A
Cl Cl
CH3
O
2,4-Dichloro acetophenone
+
Glycerol
HO OHOH
+ Br2
C8H6Cl2O189.04
C3H8O3
92.09
159.81
PTSA
n-Butanol
Cl Cl
O
O
Br
OH
C11H11BrCl2O3
342.01
+ +HBr
80.91
H2O
18.02[2-Bromomethyl-2-(2,4-dichloro-phenyl)-[1,3]dioxolan-4-
yl]-methanol
Manufacturing Process Page 124
ToR Amendment Tagoor Chemicals Private Limited
Step-B:
ClCl
O
O
Br
OOCC6H5
Cis-bromo benzoateC18H15BrCl2O4
446.12
Cl Cl
OO
Br
OH
[2-Bromomethyl-2-(2,4-dichloro-phenyl)]-[1,3]dioxolan
-4-yl]-methanol
C11H11BrCl2O3
342.01
+Benzoyl chloride
O
Cl
C7H5ClO140.57
+
Benzoic acid 2-bromomethyl-2-(2,4-dichloro-phenyl)-[1,3]dioxolan
-4-ylmethyl ester
HCl
36.46
Stage-9:
ClCl
O
O
Br
OOCC6H5
+ NN
HN
+ 1/2 K2CO3 + NaOH DMF
Water
Cis-bromo benzoateC18H15BrCl2O4
446.12
1,2,4-TriazoleC2H3N3
69.1
Potassium carbonate
69.0
Sodium hydroxide
40.0
+
C13H13Cl2N3O3
330.17
COONa
Sodium benzoate
144.10
+ KBr + 1/2 CO2 +
119.0 22.0 9.01
O
OHO
NN
N
Cl Cl
[2-(2,4-Dichloro-phenyl)-2-[1,2,4]triazol-1-ylmethyl-[1,3]dioxolan-4-yl]-methanol
C7H5NaO2
1/2 H2O
Manufacturing Process Page 125
ToR Amendment Tagoor Chemicals Private Limited
Stage-10:
ClCl
O
O
N
HO
N
N
C13H13Cl2N3O3
330.17
+ CH3SO2Cl + (C2H5)3NMDC
Water
C14H15Cl2N3O5S
408.26
+ (C2H5)3N.HCl
Methane sulfonyl chloride
114.55
Triethyl amine101.19
Triethyl amine hydrochloride
137.65
[2-(2,4-Dichloro-phenyl)-2-[1,2,4]triazol-1-ylmethyl-[1,3]dioxolan-4-yl]-methanol
ClCl
O
O
NO3SH3C
NN
1-[2-(2,4-Dichloro-phenyl)-4-ethyl-[1,3]dioxolan-2-ylmethyl]-1H-[1,2,4]triazole;
Stage-11:
ClCl
O
O
NO3SH3C
NN
C14H15Cl2N3O5S
408.26
C22H27N5O2
393.48
+ KOH
56.11
Methanol
CH3O2SOK + H2O
Methane sulfonate potassium
134.20
18.02
1-[2-(2,4-Dichloro-phenyl)-4-ethyl-[1,3]dioxolan
-2-ylmethyl]-1H-[1,2,4]triazole;(Stage-10)
+ HO N N NN
NO
CH3
CH3
2-{4-[4-(4-Hydroxy-phenyl)-piperazin-1-yl]-phenyl}-4-isobutyl-2,4-dihydro
-[1,2,4]triazol-3-one(Stage-7)
O N N NN
NO
CH3
CH3Cl Cl
OO
NN
N
+
C35H38Cl2N8O4705.63
ITRACONAZOLE
Manufacturing Process Page 126
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
Stage-2
1-(4-Methoxy-phenyl)-piperazine1-Bromo-4-Nitro-benzeneMDCMethanol
MDC recoveryMethanol recoveryEffluent water
Stage-1Palladium CarbonDMFHydrogen Gas
DMF RecoveryEffluent water
Stage-2Phenyl Chloro formateMethylene DichlorideSodium Bicarbonate
Stage-3Methylene Dichloride RecoveryEffluent water
Stage-3Hydrazine Hydrate1,4-Dioxane
Stage-41,4-Dioxane RecoveryEffluent water
Stage-4FormamidineDimethyl FormamideAcetic Acid
Dimethyl Formamide RecoveryEffluent water
Stage-52-Bromo ButanePotassium CarbonateMethanolDimethyl Formamide
Dimethyl Formamide RecoveryEffluent water
Stage-6Hydrogen BromideSodium CarbonateMethanol
Methanol recoveryEffluent water
Stage-5
Stage-6
Stage-7
Stage-8
2,4 -DichloroacetophenoneGlycerolLiq BromineBenzoyl chlorideToluene n-Butanolp-Toluenesulfonic acid
n-Butanol recoveryToluene RecoveryEffluent water
Manufacturing Process Page 127
ToR Amendment Tagoor Chemicals Private Limited
Stage-9
Stage-10
Stage-81,2,4-TriazoleSodium HydroxidePotassium CarbonateDimethyl Formamide
Dimethyl Formamide recoveryEffluent water
Stage-9Methane Sulfonyl ChlorideTriethylamineMethylene DichlorideIsopropyl Alcohol
Isopropyl alcohol RecoveryEffluent water
Stage-10Stage-7Potassium HydroxideActivated CarbonDimethyl FormamideMethanol
Stage-11Dimethyl formamide RecoveryMethanolRecoveryEffluent water
ITRACONAZOLE
Material Balance:
Material Balance of Itraconazole Stage-1
Batch Size:500.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 1-(4-Methoxy-phenyl)-piperazine
208.00 Stage-1 322.00
1-Bromo-4-Nitro-benzene 219.00 Methanol Recovery 95.00 MDC 250.00 Methanol Loss 5.00 Methanol 100.00 MDC Recovery 238.00 Water 500.00 MDC Loss 5.00 Effluent Water 500.00 (Water-500) 0 Process Emissions 87.53 (Hydrogen Bromide-87.53) 0 Organic residue 24.47 Process residue -17.47
(Distillation Residue-7 (MDC-7)
Total 1277.00 Total 1277.00
Manufacturing Process Page 128
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Itraconazole Stage-2
Batch Size:500.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 322.00 Stage-2 277.00 Palladium Carbon 5.00 DMF Recovery 665.00 DMF 700.00 DMF Loss 15.00 Hydrogen Gas 6.30 Effluent Water 337.03 Water 300.00 (Water-300,Generated Water-
37.03)
Spent Catalyst (Palladium Carbon Reuse)
5.00
Organic Residue 34.27 Process residue- 14.27
Distillation Residue-20 (DMF-20)
Total 1333.30 Total 1333.30
Material Balance of Itraconazole Stage-3
Batch Size:500.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 277.00 Stage-3 375.00 Phenyl Chloro formate 154.00 MDC Recovery 475.00 Methylene Dichloride 500.00 MDC Loss 10.00 Sodium Bicarbonate 83.00 Effluent Water 424.73 Water 350.00 (Water-350,
GeneratedWater-17.60 Sodium chloride-57.13 )
Process Emissions 43.00 (Carbon Dioxide-43) Organic Residue 36.27 Process residue-21.27
Distillation Residue-15 ( MDC)
Total 1364.00 Total 1364.00
Material Balance of Itraconazole Stage-4
Batch Size:500.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
In Kg Stage-3 375.00 Stage-4 300.00 Hydrazine Hydrate 47.00 1,4-Dioxane Recovery 475.00 1,4-Dioxane 500.00 1,4-Dioxane Loss 10.00
Manufacturing Process Page 129
ToR Amendment Tagoor Chemicals Private Limited
Water 500.00 Effluent Water 605.06 (Water-500, GeneratedWater-
17.60, Phenol-87.46)
Organic Residue 31.94 Process residue-16.94
Distillation Residue-15 (1,4-Dioxane-15)
Total 1422.00 Total 1422.00
Material Balance of Itraconazole Stage-5
Batch Size:500.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
In Kg Stage-4 300.00 Stage-5 290.00 Formamidine 39.00 DMF Recovery 238.00 Dimethyl Formamide 250.00 DMF Loss 5.00 Acetic Acid 106.00 Effluent Water 635.46 Water 500.00 (Water-500,
Ammonium acetate-135.46) 0
Organic Residue 26.54 Process residue – 19.54
Distillation Residue-7 (DMF-7)
Total 1195.00 Total 1195.00
Material Balance of Itraconazole Stage-6 Batch Size:500.00Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-5 290.00 Stage-6 320.00 2-Bromo Butane 113.00 DMF Recovery 285.00 Potassium Carbonate 57.00 DMF Loss 10.00 Methanol 450.00 Methanol Recovery 427.00 Dimethyl Formamide 300.00 Methanol Loss 9.00 Water 300.00 Effluent Water 405.44 (Water-300, Generated Water-
7.44, Potassium bromide-98) 0
Process Emissions 18.15 (Carbon Dioxide-18.15) 0 Organic Residue 35.41 (Process residue-16.41,
Distillation Residue-19 (Methanol-14, DMF-5)
Total 1510.00 Total 1510.00
Manufacturing Process Page 130
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Itraconazole Stage-7 Batch Size:500.00Kg
Stage-6 320.00 Stage-7 294.00 Hydrogen Bromide 128.00 Methanol Recovery+ Generated
Methanol 414.56
Sodium Carbonate 83.00 Methanol Loss 12.00 Methanol 400.00 Effluent Water 450.00 Water 450.00 (Water-450) 0 By product
( Sodium bromide-161.59) 161.59
Process emission 34.56 (Carbondioxide-34.56) 0 Organic residue 14.29 Process residue -6.29
Distillation Residue-8 (Methanol-8)
Total 1381 Total 1381
Material Balance of Itraconazole Stage-8 Batch Size:500.00Kg
2,4 -Dichloroacetophenone 215.00 Stage-8 370.00 Glycerol 105.00 n-Butanol Recovery 475.00 Liq Bromine 182.00 n-Butanol Loss 15.00 Benzoyl chloride 152.00 Toluene recovery 380.00 Toluene 400.00 Toluene Loss 10.00 n-Butanol 500.00 Effluent water 630.49 p-Toluenesulfonic acid 5.00 (Effluent water-600, Generated
water-20.49,Toluene-5, Paratoluene Sulfonic acid-5)
0
Water 600.00 Process Emissions 145.30 (Hydrogen bromide-92,
Hydrogen Chloride-53.30) 0
Organic residue 133.21 Process residue-118.21
Distillation Residue-15 (n-Butanol-10,Toluene-5)
Total 2159.00 Total 2159.00
Material Balance of Itraconazole Stage-9 Batch Size:500.00Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-8 370.00 Stage-9 260.00 1,2,4-Triazole 58.00 DMF Recovery 95.00
Manufacturing Process Page 131
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Itraconazole Stage-10 Batch Size:500.00Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-9 260.00 Stage-10 305.00 Methane Sulfonyl Chloride 91.00 MDC Recovery 570.00 Triethylamine 80.00 MDC Loss 12.00 Methylene Dichloride 600.00 Isopropyl Alcohol Recovery 570.00 Isopropyl Alcohol 600.00 Isopropyl Alcohol Loss 12.00 Water 500.00 Effluent Water 608.40 (Water-500,Triethylamine
Hydrochloride-108.40) 0
Organic Residue 53.60 Process residue-17.60
Distillation Residue-36 (MDC-18,IPA-18)
Total 2131.00 Total 2131.00
Material Balance of Itraconazole Stage-11 Batch Size:500.00Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-10 305.00 Itraconazole 500.00 Stage-7 294.00 Dimethyl Formamide Recovery 285.00 Potassium Hydroxide 42.00 Dimethyl Formamide Loss 10.00 Activated Carbon 8.00 Methanol Recovery 380.00 Dimethyl Formamide 300.00 Methanol Loss 12.00 Methanol 400.00 Effluent Water 613.71 Water 500.00 (Water-500,
Generated Water-13.46 Potassium Methane Sulfonate-100.25)
Spent Carbon 8.00
Sodium Hydroxide 34.00 DMF Loss 2.00 Potassium Carbonate 58.00 Effluent Water 626.97 Dimethyl Formamide 100.00 (Water-500, Generated Water-
7.47, Sodium Benzoate-119.50) 0
By product ( Potassium Bromide-98.69)
98.69
Water 500.00 Process Emission 18.24 (Carbon dioxide-18.24) 0 Organic residue 19.10 Process residue-16.1
Distillation Residue-3 (DMF-3)
Total 1120.00 Total 1120.00
Manufacturing Process Page 132
ToR Amendment Tagoor Chemicals Private Limited
Organic residue 40.29 Process residue-27.29
Distillation Residue-13 (Methanol-8, DMF-5)
Total 1849.00 Total 1849.00
KETOROLAC TROMETHAMINE
Process Description
Stage-1
5-chloro-2-benzoylpyrrole reacts with Methyl-gama-methoxy –butanoate in presence of Acetone to give Stage-1 product. Stage-2 Stage-1 Product undergoes condensation with Tromethamine in presence of Acetone to give Ketorolac Tromethamine.
Route of synthesis
Stage-1
HN Cl
O
5-Chloro-2-benzoyl pyrroleC11H8ClNO
205.64
+methyl-gama-methoxybutanoate
OCH3O
H3C
O
C6H12O3
132.16
+ NaOH
40.00
N
O
COOH
KetorolacC15H13NO3
255.27
+ NaCl
58.44
+ 2 CH3OH
64.08
Acetone
Manufacturing Process Page 133
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
N
O
COOH
KetorolacC15H13NO3
255.27
Tromethamine
NH2
HO OH
OH+
C4H11NO3
121.14
Acetone
N
O
COOH
NH2
HO OH
OH
.
ketorolac tromethamineC19H24N2O6
376.40
Flow chart:
Stage-1AcetoneTromethamineCarbon & hyflow
Stage-2 Acetone Recovery
Ketorolac Tromethamine
Stage-1
5-chloro-2-benzoylpyrroleMethyl-gama-methoxy butanonateSodium hydroxideAcetone
Acetone Recovery
Manufacturing Process Page 134
ToR Amendment Tagoor Chemicals Private Limited
KETOROLAC TROMETHAMINE
Material Balance
Material Balance of Ketorolac Tromethamine Stage-1 Batch Size: 100Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
5-chloro-2-benzoylpyrrole 59.00 Stage-1 70.00 Methyl-gama-methoxy butanonate
37.85 Acetone Recovery 475.00
Sodium hydroxide 11.45 Acetone Loss 15.00 Acetone 500.00 Methanol Recovery 16.75 Water 500.00 Effluent water 516.75 (water-500,Sodium chloride-
16.75)
Organic Residue 14.80 Process residue-4.8,
Distillation residue -10 ( Acetone-10)
Total 1108.30 Total 1108.30
Material Balance of Ketorolac Tromethamine Stage-2 Batch Size: 100Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-1 70.00 Ketorolac Tromethamine 100.00 Acetone 300.00 Acetone Recovery 285.00 Tromethamine 34.00 Acetone Loss 7.00 Carbon & hyflow 10.00 Effluent water 400.00 Water 400.00 (water-400) 0 Spent carbon & hyflow 10.00 Organic residue 12.00 Process residue-4
Distillation residue – 8 (Acetone-8)
Total 814.00 Total 814.00
Manufacturing Process Page 135
ToR Amendment Tagoor Chemicals Private Limited
LANSOPRAZOLE
Process Description
Stage-1
2, 3-Lutidine reacts with Hydrogen Peroxide and Nitric Acid in Presence of Acetic
acid to give stage-1 product.
Stage-2
Stage-1 Product reacts with 1, 1, 2- trifluoroethanol and Acetic Anhydride in
presence of Potassium Carbonate to give stage-2 product.
Stage-3
Stage-2 product undergoes chlorination with Thionyl Chloride in presence of Toluene to give stage-3 product.
Stage-4
Stage-3 product undergoes condensation with 1H-Benzoimidazole-2-thiol in
presence of Sodium Hydroxide to give stage-4 product.
Stage-5
Stage-4 product undergoes oxidation with Hydrogen peroxide in presence of IPA to
give Lansoprazole.
Manufacturing Process Page 136
ToR Amendment Tagoor Chemicals Private Limited
LANSOPRAZOLE
Route of Synthesis:
Stage-1
2,3-Lutidine
107.15
+
H2O2
34.00
+ HNO3
63.00
+ 2 H2O
C7H9N
36.044-Nitro-2,3-Dimethyl pyridine-N-Oxide
168.15
C7H8N2O3
N+
O-
H3C
H3C
NO2
NCH3
CH3
Hydrogen Peroxide
HO OH
Stage-2
+
4-Nitro-2,3-Dimethyl pyridine-N-Oxide
168.15
CF3CH2OH
+ K2CO3+
C4H6O3
+ + HCl
100.04 102.09
N
OCH2CF3
CH3
CH2OH
. HCl
257.64
+ KHCO3
100.12
+ KNO2
85.10
+CH3COONa
82.03
CH3COOH
C7H8N2O3
C9H11ClF3NO2
OO
OOHF
F
F
N+
O-
H3C
H3C
NO2
1,1,2-Trifluoro-ethanol Acetic anhydride 138.21
NaOH
40.00 36.46
60.05
+
[3-Methyl-4-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-methanol
Manufacturing Process Page 137
ToR Amendment Tagoor Chemicals Private Limited
Stage-3
N
OCH2CF3
CH3
CH2OH
. HCl
257.64
+
C9H11ClF3NO2
[3-Methyl-4-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-methanol
+
SOCl2
Thionyl chloride
118.97
N
OCH2CF3
CH3
CH2Cl
. HCl
276.08
SO2
64.06
+ HCl
36.46
C9H10Cl2F3NO
S
O
Cl
Cl
2-Chloromethyl-3-methyl-4-(2,2,2-trifluoro-ethoxy)-pyridine Hydrochloride
Stage-4
N
OCH2CF3
CH3
CH2Cl
. HCl
276.08
C9H10Cl2F3NO
2-Chloromethyl-3-methyl-4-(2,2,2-trifluoro-ethoxy)-pyridine Hydrochloride
+N
HN
HS + 2 NaoH
80.00
150.20
N
OCH2CF3
CH3
CH2 SN
HN
+ 2 NaCl
116.88
+ 2 H2O
36.04
C7H6N2S
C16H14F3N3OS
353.36
1H-Benzoimidazole-2-thiol
2-[3-Methyl-4-(2,2,2-trifluoro-ethoxy)-pyridin-2-ylmethylthio]-1H-benzo[d]imidazole
Manufacturing Process Page 138
ToR Amendment Tagoor Chemicals Private Limited
Stage-5
N
OCH2CF3
CH3
CH2 SN
HN
+
C16H14F3N3OS
353.36
2-[3-Methyl-4-(2,2,2-trifluoro-ethoxy)-pyridin-2-ylmethylthio]-1H-benzo[d]imidazole
+
H2O2
Hydrogen peroxide
N
OCH2CF3
CH3
CH2 SN
HN
O
Lansoprazole
369.36
H2O
18.02C16H14F3N3O2S
HO OH
34.01
Manufacturing Process Page 139
ToR Amendment Tagoor Chemicals Private Limited
LANSOPRAZOLE
Flow Chart:
Stage-1
Stage-2
Stage-3
Stage-4
Stage-5
2,3-LutidineAcetic AcidHydrogen Peroxide (50%)Sulfuric AcidNitric Acid Effluent water
Stage-1Sodium HydroxidePotassium Carbonate1,1,2-Tri Fluoro EthanolMIBKAcetic AnhydrideTEBACTolueneHydrogen Chloride Activated Carbon
Stage-2Methylene DichlorideTolueneThionyl Chloride
Stage-3Sodium Hydroxide1H-Benzoimidazole-2thiol
Stage-4Isopropyl AlcoholHydrogen Peroxide (50%)CatalystChloroformAcetone
Isopropyl alcohol RecoveryAcetone recoveryEffluent water
Effluent water
Toluene recoveryMethylene Dichloride RecoveryEffluent water
MIBK RecoveryToluene RecoveryEffluent water
LANSOPRAZOLE
Manufacturing Process Page 140
ToR Amendment Tagoor Chemicals Private Limited
LANSOPRAZOLE
MATERIAL BALANCE:
Material Balance of Lansoprazole Stage-1
Batch Size:500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 2,3-Lutidine 188.00 Stage-1 280.00 Acetic Acid 46.00 Spent Sulfuric Acid 50.00 Hydrogen Peroxide (50%) 120.00 Effluent water 969.23 Sulfuric Acid 50.00 (Water-800, Generatedwater-
63.23,water from hydrogen peroxide-60, Acetic Acid - 46)
0
Nitric Acid 111.00 Organic Residue 15.77 Water 800.00 Process residue – 15.77 Total 1315.00 Total 1315.00
Material Balance of Lansoprazole Stage-2
Batch Size:500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 280.00 Stage-2 405.00 Sodium Hydroxide 67.00 MIBK Recovery 140.00 Potassium Carbonate 230.00 MIBK Loss 5.00 1,1,2-Tri Fluoro Ethanol 167.00 Toluene Recovery 380.00 MIBK 150.00 Toluene Loss 10.00 Acetic Anhydride 170.00 Effluent Water 1041.59 TEBAC 1.00 (Water-800, Sodium Acetate-136.59,
Acetic Acid-100,Toluene-5) 0
Toluene 400.00 Inorganic solid waste 308.70 Hydrogen Chloride 61.00 (Potassium Nitrite-141.70, Potassium
Bicarbonate-167) 0
Activated Carbon 5.00 Spent Carbon 5.00 Water 800.00 Organic Residue 35.71 Process Residue-25.71
Distillation Residue-10 (MIBK-5,Toluene-5)
Total 2331.00 Total 2331.00
Manufacturing Process Page 141
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Lansoprazole Stage-3
Batch Size:500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 405.00 Stage-3 415.00 Methylene Dichloride 400.00 Toluene Recovery 475.00 Toluene 500.00 Toluene Loss 15 Thionyl Chloride 180.00 Methylene Dichloride Recovery 380.00 Methylene Dichloride Loss 12.00 Process Emissions 152.68 (Sulfur Dioxide-97.50,Hydrogen
Chloride-55.18) 0
Organic Residue 35.32 Process residue- 17.32
Distillation Residue-18 (Toluene-10, Methylene Dichloride -8)
Total 1485.00 Total 1485.00
Material Balance of Lansoprazole Stage-4
Batch Size:500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 415.00 Stage-4 505.00 Sodium Hydroxide 121.00 Effluent Water 829.88 1H-Benzoimidazole-2thiol 226.00 (Water-600, Generated Water-
54.18,Sodium Chloride-175.70) 0
Water 600.00 Organic Residue 27.12 (Process Residue-27.12) Total 1362.00 Total 1362.00
Manufacturing Process Page 142
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Lansoprazole Stage-5
Batch Size:500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-4 505.00 Lansoprazole 500.00 Isopropyl Alcohol 250.00 Isopropyl Alcohol Recovery 238.00 Hydrogen Peroxide (50%) 98.00 Isopropyl Alcohol Loss 5.00 Catalyst 1.00 Chloroform Recovery 384.00 Chloroform 400.00 Chloroform Loss 12.00 Acetone 150.00 Acetone Recovery 143.00 Water 600.00 Acetone Loss 3.00 Effluent Water 674.75 (Water-600, Generated Water-
25.75, Water from Hydrogen peroxide-49)
0
Catalyst Reuse 1.00 Organic Residue 43.25 Process residue-28.25
Distillation residue-15 (IPA-7, Chloroform-4,Acetone-4)
Total 2004.00 Total 2004.00
Manufacturing Process Page 143
ToR Amendment Tagoor Chemicals Private Limited
LOPERAMIDE HCL Process Description:
Stage-1: Diphenyl acetonitrile reacts with 1, 2-Dichloroethane in presence of TBAB, Toluene and Methanol to give Stage-1 Product.
Stage-2: Stage-1 product reacts with Sulphuric acid and water in presence of Acetic acid and IPA to give Staeg-2 product.
Stage-3: Stage-2 Product reacts with Hydrobromic acid in presence of Acetic acid to give Stage-3 Product.
Stage-4:
Stage-3 product reacts with Thionyl chloride in presence of Toluene to give Stage-4 product.
Stage-5:
Stage-4 Product reacts with Dimethyl amine in presence of Toluene, water to give Stage-5 product.
Stage-6:
Step-A:
4-Chloro Phenyl magnesium bromide reacts with 4-oxo-piperidine-1-carboxylic acid ethyl ester in presence of Toluene and Hydrobromic acid to give Step-A Product.
Step-B:
Step-A Product reacts with Sodium hydroxide in presence of Methanol, Toluene to give Stage-6 Product.
Stage-7:
Stage-5 reacts with stage-6 in presence of Potassium Carbonate, Potassium Iodide and acetone to give stage-7 Product.
Stage-8:
Stage-7 Product undergoes Salt formation with Hydrochloric acid in presence of Acetone to give Loperamide Hydrochloride.
Route of Synthesis.
Manufacturing Process Page 144
ToR Amendment Tagoor Chemicals Private Limited
Stage-1
N
ClCl
Diphenyl-acetonitrile
C14H11N
193.24
+
98.96
N
Cl
HCl+
C16H14ClN
255.74
TBAB
1,2-Dichloro-ethane 4-Chloro-2,2-diphenyl-butyronitrile
C2H4Cl2
36.46
Stage-2
N
Cl
C16H14ClN
255.74
+ H2SO4
Sulphuric acid98.08
O
O
NH4Cl +
3,3-Diphenyl-dihydro-furan-2-oneC16H14O2
238.28
53.49
+ SO2
64.06
Acetic acid
4-Chloro-2,2-diphenyl-butyronitrile
+ H2O
18.0
+ 1/2 O2
16.0
Manufacturing Process Page 145
ToR Amendment Tagoor Chemicals Private Limited
Stage-3 O
O
3,3-Diphenyl-dihydro-furan-2-one
C16H14O2
238.28
HO
O
Br
4-Bromo-2,2-diphenyl-butyric acid (Loperamide-III)
C16H15BrO2
319.19
+ HBr
80.91
CH3COOH
Stage-4:
OH
O
Br
4-Bromo-2,2-diphenyl-butyric acid (Loperamide-III)
C16H15BrO2
319.19
+ SOCl2
Thionyl chloride
Toluene + SO2 + HCl
118.97
COCl
Br
4-Bromo-2,2-diphenyl-butyryl chloride
C16H14BrClO
337.64
36.4664.06
Stage-5:
COCl
Br
4-Bromo-2,2-diphenyl-butyryl chloride
C16H14BrClO
337.64
Dimethylamine
Toluene
Water
+HN
CH3H3C
C2H7N
45.08
N
O
BrCH3
H3C
346.26
4-Bromo-N,N-dimethyl-2,2-diphenyl-butyramide
C18H20BrNO
+ HCl
36.46(Dihydro-N,N-dimethyl-3,3-diphenyl
-2(3H)-furaniminium bromide)
or
Manufacturing Process Page 146
ToR Amendment Tagoor Chemicals Private Limited
Stage-6:
Step-A:
BrMg Cl
4-Chloro phenyl magnesium bromide
C6H4BrClMg
215.76
+ NO COOC2H5
4-Oxo-piperidine-1-carboxylic acid ethyl ester
C8H13NO3
171.19
Toluene,HCl solution
4-(4-Chloro-phenyl)-4-hydroxy-piperidine-1-
carboxylic acid ethyl ester
C14H18ClNO3
283.75
+ MgBr2
+ HBr
80.91
184.11
Cl N COOC2H5
HO
Step-B:
4-(4-Chloro-phenyl)-4-hydroxy-piperidine-1-
carboxylic acid ethyl ester
C14H18ClNO3
283.75
Cl N COOC2H5
HO
+ NaOH
40.00
+ HCl
36.46
Methanol,Toluene
4-(4-Chlorophenyl)-4-hydroxy piperidine
C11H14ClNO
211.69
+ C2H5OH
Ethanol46.07
+ CO2
44.01NaCl
58.44+Cl NH
HO
Manufacturing Process Page 147
ToR Amendment Tagoor Chemicals Private Limited
Stage-7:
N
O
BrCH3
H3C
346.26
C18H20BrNO
+ 4-(4-Chloro-phenyl)-piperidin-4-ol
K2CO,KI
AcetoneHN
OH
Cl
C11H14ClNO211.69
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-N,N-dimethyl-2,2-diphenyl-butyramide
ON
N
OH
Cl
C29H33ClN2O2
477.04
+ HBr
80.91
4-Bromo-N,N-dimethyl-2,2-diphenyl-butyramide
(Dihydro-N,N-dimethyl-3,3-diphenyl-2(3H)-
furaniminium bromide)or
Stage-8:
Loperamide Hydrochloride4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-N,N-dimethyl-
2,2-diphenyl-butyramide
ON
N
OH
Cl
C29H34Cl2N2O2
513.50C29H33ClN2O2
477.04
+ HCl
36.46
ON
N
OH
Cl
HCl
Acetone
.
Manufacturing Process Page 148
ToR Amendment Tagoor Chemicals Private Limited
Flowchart: Di phenyl acetonitrile1,2-Dichloro ethaneTBABC.S.LYEAcetic acidToluene Methanol
Stage-1Methanol RecoveryToluene RecoveryEffluent water
Stage-2 Isopropyl alcohol RecoveryEffluent water
Acetic AcidSulfuric acidSoda ash (10%)Isopropyl alcohol
Stage-3Toluene RecoveryEffluent water
HBr In Acetic acid (40%)Toluene
Stage-4Toluene RecoveryEffluent water
Thionyl chlorideToluene
Stage-5 Toluene RecoveryEffluent water
Sodium carbonateDimethylamineToluene
Stage-6Toluene RecoveryMethanol RecoveryEffluent water
4-Chloro Phenyl Magnesium BromideHydrobromic acidSodium HydroxideHydrochloric acidMethanolToluene
4-(4-Chloro-phenyl)-piperidin-4-olPotassium IodidePotassium carbonateActivated CarbonAcetone
Acetone recoveryEffluent water
Hydrochloric acidAcetone Acetone Recovery
Stage-7
Stage-8
LOPERAMIDE HCL
Manufacturing Process Page 149
ToR Amendment Tagoor Chemicals Private Limited
LOPERAMIDE HCL
Material Balance:
Material balance of Loperamide HCl Stage-1 Batch Size: 200.0 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Di phenyl acetonitrile 114.00 Stage-1 142.00 1,2-Dichloro ethane 260.00 Dichloro ethane Recovery 190.00 TBAB 6.00 Dichloro ethane Loss 5.00 C.S.LYE 15.00 Toluene Recovery 285.00 Acetic acid 0.50 Toluene Loss 5.00 Toluene 300.00 Methanol recovery 190.00 Methanol 200.00 Methanol Loss 5.00 Water 500.00 Effluent water 526.50 (Water-500,Acetic acid-
0.5,C.S.lye-15, TBAB-6, Toluene-5)
Process emission 21.50 (Hydrogen Chloride-21.50) Organic Residue 25.50 Process residue-9.5,
Distillation residue-16 (Dichloro ethane -6,Toluene-5,Methanol-5)
Total 1395.50 Total 1395.50
Material balance of Material balance of Loperamide HCl Stage-2 Batch Size: 200.0 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-1 142.00 Stage-2 125.00 Acetic Acid 55.00 Effluent water 474.70 Sulfuric acid 55.00 (Water-290, Acetic acid-
55, soda ash solution-100, Ammonium chloride-29.70)
Soda ash (10%) 100.00 Isopropyl alcohol Recovery
143.00
Isopropyl alcohol 150.00 Isopropyl alcohol Loss 5.00 Water 300.00 Process Emission 44.44 (Sulphur dioxide-35.56,
Oxygen-8.88)
Organic Residue 9.86 Process residue-7.86
Manufacturing Process Page 150
ToR Amendment Tagoor Chemicals Private Limited
Distillation residue-2 (Isopropyl alcohol-2)
Total 802.00 Total 802.00
Material balance of Material balance of Loperamide HCl Stage-3 Batch Size: 200.0 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-2 125.00 Stage-3 160.00 HBr In Acetic acid (40%) 108.00 Toluene Recovery 238.00 Toluene 250.00 Toluene Loss 7.00 Water 300.00 Effluent water 369.80 (Water-300, Acetic acid-
64.8,Toluene-5)
Organic Residue 8.20 Process residue-3.2,
Distillation residue-5 (Toluene-5)
Total 783.00 Total 783.00
Material Balance of Loperamide HCl Stage-4 Batch Size:200Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-3 160.00 Stage-4 160.00 Thionyl chloride 60.00 Toluene recovery 190.00 Toluene 200.00 Toluene loss 5.00 Process Emission 50.38 (Sulphur dioxide-32.11,
Hydrogen Chloride-18.27
Organic residue 14.62 Process residue-9.62
Distillation residue-5 (Toluene-5)
Total 420.00 Total 420.00
Material Balance of Loperamide HCl Stage-5 Batch Size:200Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-4 160.00 Stage-5 152.00 Sodium carbonate 40.00 Toluene Recovery 190.00 Dimethylamine 26.00 Toluene Loss 5.00 Toluene 200.00 Effluent Water 343.00
Manufacturing Process Page 151
ToR Amendment Tagoor Chemicals Private Limited
Water 300.00 (Water-300,Sodium Carbonate-40,Toluene-3)
Process emission 17.27 (Hydrogen Chloride-17.27) Organic residue 18.73 Process residue-16.73
Distillation residue-2 (Toluene-2)
Total 726.00 Total 726.00
Material Balance of Loperamide HCl Stage-6 Batch Size:200Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
4-Chloro Phenyl Magnesium Bromide
106.00 Stage-6 94.00
4-Oxo-Piperidine-1-Carboxylic acid ethyl ester
85.00 Methanol Recovery 285.00
Hydrobromic acid 40.00 Methanol Loss 10.00 Sodium Hydroxide 19.00 (Mixed solvent)
Toluene Recovery + Generated Ethanol
576.59
Hydrochloric acid 18.00 Toluene Loss 5.00 Methanol 300.00 Effluent water 520.84 Toluene 565.00 (Water-400, Magnesium
Bromide-90.45,Sodium Chloride-27.39,Toluene-3)
0
Water 400.00 Process emission 20.62 (carbondioxide-20.62) 0 Organic residue 20.95 Process residue-13.95
Distillation residue-7 (Methanol-5,Toluene-2)
Total 1533 Total 1533
Material Balance of Loperamide HCl Stage-7: Batch Size:200Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-6 152.00 Stage-7 200.00 4-(4-Chloro-phenyl)- piperidin-4-ol
94.00 Acetone recovery 190.00
Potassium Iodide 20.00 Acetone loss 5.00 Potassium carbonate 40.00 Effluent Water 460.00 Activated Carbon 10.00 (Water-400,Potassium
Iodide-20, Potassium Carbonate-40)
Manufacturing Process Page 152
ToR Amendment Tagoor Chemicals Private Limited
Acetone 200.00 Spent carbon 10.00 Water 400.00 Process emission 35.52 (Hydrogen Bromide-35.52 Organic Residue 15.48 Process residue-10.48
Distillation residue-5 (Acetone-5)
Total 916.00 Total 916.00
Material Balance of Loperamide HCl Stage-8: Batch Size:200Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-7 200.00 Loperamide HCl 200.00 Hydrochloric acid 15.00 Acetone recovery 190.00 Acetone 200.00 Acetone loss 5.00 Organic residue 20.00 Process residue-15
Distillation residue-5 (Acetone-5)
Total 415.00 Total 415.00
LOSARTAN POTASSIUM Process Description Stage-1 Orthototylbenzonitrile and Sodium nitrate reacts with Sodium azide and sodium nitrite
in presence of Toluene and Hcl to give Stage-1 product.
Stage-2
Stage-1 product reacts with trityl chloride in presence of MDC to give Stage-2
product.
Stage-3
Stage-2 product undergoes bromination with N-Bromasuccinimiode in presence of
MDC and Ethyl acetate to give stage-3 product.
Stage-4
Stage-3 product undergoes condensation eith Butyl Chloroformyl imidazole in
presence of Sodium hydroxide and Methanol to give Stage-4 product..
Stage-5
Stage-4 product undergoes salt formation with POTASSIUM Hydroxide in presence of Methanol to give Losartan potassium.
Manufacturing Process Page 153
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis: Stage-1
Ortho tolylbenzonitrile
CN
CH3
+
Sodium Azide
NaN3 + NaNO2 + 2 HCl
CH3
N N
NHN
5-(4'-Methyl-biphenyl-2-yl)-2H-tetrazole
Sodium nitrite Hydrochloric Acid
C14H11N
193.24
65.0 69.0 2X36.46=72.92 C14H12N4
236.27
+ 2 NaCl + H2O + N2
2X58.44=116.89 18.0 28.0 Stage-2
CH3
N N
NHN
5-(4'-Methyl-biphenyl-2-yl)-2H-tetrazole
C14H12N4
236.27
+
trityl chloride
Cl + HCl
5-(4'-Methyl-biphenyl-2-yl)-2-trityl-2H-tetrazole
36.46
CH3
N N
NN
C19H15Cl
278.78
C33H26N4
478.59
Manufacturing Process Page 154
ToR Amendment Tagoor Chemicals Private Limited
Stage-3
5-(4'-Methyl-biphenyl-2-yl)-2-trityl-2H-tetrazole
CH3
N N
NN
C33H26N4478.59
+
N-Bromosuccinimide
OO N
Br
CH2Br
N N
NN
5-(4'-Bromomethyl-biphenyl-2-yl)-2-trityl-2H-tetrazole
C4H4BrNO2177.98
C33H25BrN4 557.48
OOHN
+
Succinimide
C4H5NO299.09
Stage-4
CH2Br
N N
NN
5-(4'-Bromomethyl-biphenyl-2-yl)-2-trityl-2H-tetrazole
C33H25BrN4 557.48
NH
N
ClCH3
HO+
HO
N
NHN
N N
N
Cl
+ NaOH
Sodium hydroxide
+
trityl alcohol
OH
Losartan Base
+ NaBr
Sodium bromide
C22H23ClN6O 422.91
C19H16O260.33
102.89
40.0C8H13ClN2O
188.65
Butylchloroformyl imidazole
Manufacturing Process Page 155
ToR Amendment Tagoor Chemicals Private Limited
Stage-5
HO
N
NHN
N N
N
Cl
Losartan Base
C22H23ClN6O 422.91
+ KOH
HO
N
NKN
N N
N
Cl
C22H22ClKN6O 461.00
Losartan PotassiumPotassium hydroxide
56.11
+ H2O
18.0 Flow Chart:
Stage-1
Stage-2
Stage-3
Ortho tolylbenzonitrileSodium AzideHydrochloric acidSodium nitriteToluene
Toluene RecoveryEffluent water
Stage-1Trityl chlorideTEAMDCMethanol
MDC RecoveryMethanol RecoveryEffluent water
Stage-2N-Bromosuccinimide (NBS)Sodium meta bisulphateMethylenedichlorideEthyl Acetate
Methylene dichlorie RecoveryEthyl acetate RecoveryEffluent water
LOSARTAN POTASSIUM
Stage-4
Stage-3Butyl chloro formyl imidazole TBABMethanolSodium hydroxide
Methanol RecoveryEffluent water
Stage-5Methanol RecoveryEffluent water
Stage-4Potassium hydroxideMethanolActivated Carbon
Manufacturing Process Page 156
ToR Amendment Tagoor Chemicals Private Limited
LOSARTAN POTASSIUM
Material Balance:
Material Balance Of Losartan Potassium Stage-1
Batch Size:100kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Ortho tolylbenzonitrile 62.00 Stage-1 70.00
Sodium Azide 20.85 Toluene Recovery 380.00 Hydrochloric acid 23.50 Toluene Loss 8.00 Sodium nitrite 22.15 Effluent water 645.21 Toluene 400.00 (Water-600,
Generated water-5.76, Sodium chloride-37.45, Toluene-2)
0
Water 600.00 Process Emission 8.92 (Nitrogen-8.92) 0 Organic Residue 16.37 Process residue-6.37
Distillation Residue-10 (Toluene-10)
Total 1128.50 Total 1128.50
Material Balance Of Losartan Potassium Stage-2
Batch Size:100kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 70.00 Stage-2 130.00 Trityl chloride 82.50 MDC Recovery 475.00 TEA 30.00 MDC Loss 10.00 MDC 500.00 Methanol Recovery 475.00 Methanol 500.00 Methanol Loss 10.00 Water 500.00 Effluent Water 530.00 (Water-500,TEA-30) 0 Process emission 10.78 (Hydrogen chloride-10.78) 0 Organic Residue 41.72 Process residue-11.72
Distillation Residue-30 (Methanol-15,MDC-15)
Total 1682.50 Total 1682.50
Manufacturing Process Page 157
ToR Amendment Tagoor Chemicals Private Limited
Material Balance Of Losartan Potassium Stage-3
Batch Size:100kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 130.00 Stage-3 140.00 N-Bromosuccinimide (NBS) 48.25 Methylenedichloride
Recovery 380.00
Sodium meta bisulphate 10.00 Methylenedichloride Loss 8.00 Methylenedichloride 400.00 Ethyl Acetate Recovery 190.00 Ethyl Acetate 200.00 Ethyl Acetate Loss 4.00 Water 600.00 Effluent Water 613.00 (Water-600,
Sodium meta bisulphate-10, Ethyl acetate-3,)
0
Organic Residue 53.25 Process residue-38.25
(Organic impurities-11.34 succinimide-26.91) Distillation Residue-15 (Ethyl acetate-3,MDC-12)
Total 1388.25 Total 1388.25
Material Balance Of Losartan Potassium Stage-4
Batch Size:100kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 140.00 Stage-4 99.00 Butyl chloro formyl imidazole (BCFI)
47.35 Methanol Recovery 760.00
TBAB 5.00 Methanol Loss 20.00 Methanol 800.00 Effluent Water 730.76 Sodium hydroxide 9.95 (Water-700,
Sodium bromide-25.76, TBAB-5)
0
Water 700.00 By-Product 65.24 (trityl alcohol-65.24) 0 Organic Residue 7.30 Process residue- 7.30
Distillation Residue-20 (Methanol-20)
Total 1702.3 Total 1695
Manufacturing Process Page 158
ToR Amendment Tagoor Chemicals Private Limited
Material Balance Of Losartan Potassium Stage-5:
Batch Size:100kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-4 99.00 Losartan Potassium 100.00 Potassium hydroxide 13.05 Methanol Recovery 380.00 Methanol 400.00 Methanol Loss 10.00 Activated Carbon 15.00 Effluent Water 406.15 Water 400.00 (Water-400,
Generated water-4.15) 0
Spent Carbon 15.00 Organic Residue 15.90 Process residue-5.90
Distillation residue-10 (Methanol-10)
Total 927.05 Total 927.05
NEBIVOLOL HYDROCHLORID
Process Description:
Stage-1:
(R)-2-(benzyl amino)-1-(6-fluro-3, 4-dihydro-2H-chromen-2-yl) ethanol react with 6-Fluro-3, 4-dihydro-2-(oxiran-2- yl)-2H chromene in presence of diisopropylethylamine, Methanol,HCl to form NBL/Stage-1.
Stage-2:
NBL/Stage-I reacts with Pd/C in presence of methanol and treated with IPA HCL to form Nebivolol hydrochloride Pharma (Stage-2).
Manufacturing Process Page 159
ToR Amendment Tagoor Chemicals Private Limited
Route of synthesis
Stage-1
O
F
O
F
N O
F
MethanolO
F
NH
OH
(R)-2-(benzylamino)-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol
OH
OH
O
6-fluoro-3,4-dihydro-2-((R)-oxiran-2-yl)-2H-chromene
HCl
HCl+ HCl
36.5
2-{Benzyl-[2-(6-fluoro-chroman-2-yl)-2-hydroxy-ethyl]-amino}-
1-(6-fluoro-chroman-2-yl)-ethanol Hydrochloride
C18H20FNO2
301.36
C11H11FO2194.2
C29H32ClF2NO4
532.02
Stage-2
O
F
HN O
FPd/C, MeoHIPA HCl
Nebivolol Hydrochloride
C22H25F2NO4 HCL
CH3
Toluene
HCl OH
OHO
F
N O
F
OH
OHHCl
2-{Benzyl-[2-(6-fluoro-chroman-2-yl)-2-hydroxy-ethyl]-amino}-
1-(6-fluoro-chroman-2-yl)-ethanol Hydrochloride
+ H2
2.00
C29H32ClF2NO4
532.02
C7H8
92.14
442.03
Manufacturing Process Page 160
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart
Stage-1
Stage-2
NEBIVOLOL HYDROCHLORIDE
(R)-2-(benzyl amino)-1-(6-fluro-3,4-dihydro-2H-chromen-2-yl) ethanol6-Fluro-3,4-dihydro-2-(oxiran-2- yl)-2HchromeneDiiso propyl etherMethanol
Methanol Rec
Stage-1MethanolPd/carbon
Methanol Rec
Material Balance
Material Balance of Nebivolol Hydrochloride Stage-1
BatchSize:200.0Kg Name of the input Quantity in
Kg Name of the out put Quantity in
Kg (R)-2-(benzyl amino)-1-(6-fluro-3,4-dihydro-2H-chromen-2-yl) ethanol
169.00 Stage-1 268.00
6-Fluro-3,4-dihydro-2-(oxiran-2- yl)-2Hchromene
108.85 Methanol Recovery
550.00 Diiso propyl ether 400.00 Methanol Loss 30.00 Methanol 600.00 Diiso propyl ether
Recovery 380.00
Hydrochloric acid 20.45 Diiso propyl ether Loss 20.00 Organic Residue 50.30 Process residue -30.3,
Distillation residue -20 Methanol-20)
Total 1298.30 Total 1298.30
Manufacturing Process Page 161
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Nebivolol Hydrochloride Stage-2
BatchSize:200.0Kg Name of the input Quantity in
Kg Name of the out put Quantity in
Kg Stage-1
268.00 Nebivolol Hydrochloride 200.00
Methanol 800.00 Mixed solvent (Methanol Recovery + Toluene Recovery)
806.36
Pd/carbon 2.00 Methanol Loss 20.00 Hydrogen 0.80 Pd/carbon Recovery 2.00 IPA HCl 80.00 IPA Recovery 50.00 IPA Loss 30.00 Organic residue 42.44 Process residue -22.44
Distillation residue-20 (Methanol-20)
Total 1150.80 Total 1150.80
NORTRIPTYLINE HYDROCHLORIDE
Process Description:
Stage-1:
[3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-dimethyl-amine Hydrochloride reacts with ethyl chloro formate in presence of Sodium Hydroxide and toluene to give Stage-1 product.
Stage-2:
Stage-1 Product undergoes Hydrolysis with Potassium Hydroxide in presence of Isopropyl alcohol an Hydrochloric acid to give Stage-2 product.
Stage-3:
Stage-2 product undergoes Salt formation in presence of IPA.HCl and Acetone to give Nortriptyline Hydrochloride.
Manufacturing Process Page 162
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis
Satge-1:
NCH3
CH3
. HCl
[3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)
-propyl]-dimethyl-aminehydrochloride
C20H24ClN
313.86
Ethyl chloroformate
O
O Cl+
C3H5ClO2
108.52
+ NaOH
40.00
+
Sodium Sulphate, Toluene , DM water
NaCl
58.44
+ HCl
36.46
NCH3
O
O
CH3
[3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-methyl-carbamic acid
ethyl esterC22H25NO2
335.44
+ CH3OH
32.04
Manufacturing Process Page 163
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
N
CH3
O
O
CH3
[3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-methyl-carbamic acid
ethyl ester
C22H25NO2
335.44
Chloroform, Isopropylalcohol
+ KOH
56.11
+ HCl
36.46
NH
CH3
[3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-
methyl-amineC19H21N
263.38
+
Methyl formate
OOH3C
C2H4O2
60.05
+ KCl
74.55
+ CH3OH
32.04
+
H2O+
18.02
0.5 O2
16.00
Stage-3
Acetone, Activated carbon
NH
CH3
[3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-
methyl-amineC19H21N
263.38
NH
CH3
. HCl
Nortriptyline HCl
C19H22ClN
299.84
+ HCl
36.46
Manufacturing Process Page 164
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
Stage-2
[3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-dimethyl-amine HydrochlorideEthyl chloroformateSodium hydroxideSodium sulphateToluene
Toluene RecoveryEffluent water
Stage-1Potassium HydroxideHydrochloric acidChloroform IPA
IPA RecoveryEffluent water
Stage-3
Stage-2Hydrochloric AcidAcetone Activated carbon
Acetone RecoveryEffluent water
NORTRIPTYLINE HYDROCHLORIDE
Manufacturing Process Page 165
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of Nortriptyline Hydrochloride Stage-1
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg [3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-dimethyl-amine Hydrochloride
240.00
Stage-1 245.00
Ethyl chloroformate 83.00 Toluene Recovery 385.00 Sodium hydroxide 31.00 Toluene Loss 10.00 Sodium sulphate 20.00 Effluent water 472.50 Toluene 400.00 (water-400,Sodium chloride-
45,Methanol-24.5,Toluene-3) 0
Water 400.00 Inorganic solid waste 20.00 (Sodium sulphate-20) 0 Process emission 28.00 (Hydrogen Chloride-28) 0 Organic residue 13.50 Process residue -11.5
Distillation residue-2 (Toluene-2)
Total 1174.00 Total 1174.00
Material Balance of Nortriptyline Hydrochloride Stage-2
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 245.00 Stage-2 183.00 Potassium Hydroxide 41.00 Chloroform Recovery 385.00 Hydrochloric acid 27.00 Chloroform Loss 15.00 Chloroform 400.00 IPA Recovery 385.00 IPA 400.00 IPA Loss 10.00 Water 400.00 Effluent water 507.85 (water-386,Potassium chloride-
54.45,Methyl formate-44,Methanol-23.40)
0
Process emission 12.00 (Oxygen-12) 0 Organic residue 15.15 Process residue -10.15
Distillation residue-5 (IPA-5)
Total 1513.00 Total 1513.00
Manufacturing Process Page 166
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Nortriptyline Hydrochloride Stage-3
Batch Size: 200.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 183.00 Nortriptyline Hydrochloride 200.00 Hydrochloric Acid 26.00 Acetone Recovery 190.00 Acetone 200.00 Acetone Loss 5.00 Activated carbon 5.00 Effluent water 300.00 Water 300.00 (water-300) Spent carbon recovery 5.00 Organic residue 14.00 Process residue -9
Distillation residue-5 (Acetone-5)
Total 714.00 Total 714.00
N-TERT-BUTOXYCARBONYL-4-HYDROXY PIPERIDINE
Process Description:
Stage-1:
N-Carbethoxy-4-Piperidone reacts with Di-tert butyl dicarbonate in presence of water Toluene to give N-Tert-Butoxycarbonyl-4-Hydroxy Piperidine.
Manufacturing Process Page 167
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
O
O
O
O
OCH3
H3C CH3
H3C
H3C CH3
+
N-Carbethoxy-4-piperidone
NOO
O
N-tert butoxy carbonyl-4-hydroxy piperidine
NHO
O
O
CH3
CH3
CH3
C8H13NO3
171.19
Di-tert butyl dicarbonateC10H18O5
218.25
C10H19NO3
201.26
+ O
O
O
O
HO CH3
H3C CH3
C6H10O5
162.14
+ C2H5OH
Ethanol46.07
+ 2 H2O
36.03
+ 0.5 O2
16.00
Water
Tert butyl pyrocarbonate
Flowchart:
Stage-1
N-TERT-BUTOXYCARBONYL-4-HYDROXY PIPERIDINE
N-Carbethoxy-4-amino piperidinedi-tert butyl dicarbonateToluene
Toluene RecoveryEffluent water
Material Balance:
Material Balance of N-Tert-Butoxycarbonyl-4-Hydroxy Piperidine. Stage-1 Batch Size: 100.00 Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
N-Carbethoxy-4-amino piperidine 90.00 N-Tert-Butoxycarbonyl-4-Hydroxy Piperidine.
100.00
di-tert butyl dicarbonate 114.66 Toluene Recovery 385.00 Toluene 400.00 Toluene Loss 10.00 Water 400.00 Effluent water 493.53 (Water-381.10, Ethanol-
24.20,Toluene-3, Tert butyl pyrocarbonate-85.23)
0
Manufacturing Process Page 168
ToR Amendment Tagoor Chemicals Private Limited
Process emission 8.37 (Oxygen-8.37) 0 Organic residue 7.76 Process residue – 5.76
Distillation residue-2 (Toluene-2)
Total 1004.66 Total 1004.66
OMEPRAZOLE MAGNESIUM DIHYDRATE
Process Description:
Stage-1:
Omeprazole reacts with Ammonium hydroxide and Magnesium sulfates to give Omeprazole Magnesium dihydrate.
Route of Synthesis:
Stage-1:
N
OCH3
H3C CH3
SNH
N OCH3O
OmeprazoleC17H19N3O3S
2X345.41=690.82
2 + NH4OH
35.04
+ MgSO4
120.36
N
OCH3
H3C CH3
SN-
N OCH3OMg+2 2H2O
2
+ (NH4)2SO4
132.13Ammonium sulfate
749.12
Omeprazole Magnesium Dihydrate
C17H18N3O3S.Mg+2.2H2O
Ammonium hydroxide Magnesium sulphate
Manufacturing Process Page 169
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
Omeprazole Ammonium hydroxide (20%)Magnesium sulfateActivated carbon
OMEPRAZOLE MAGNESIUM DIHYDRATE
Effluent water
Material Balance:
Material Balance Of Omeprazole Magnesium Dihydrate Stage-1
Batch Size: 100.0Kgs Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Omeprazole 103.00 Omeprazole Magnesium
Dihydrate 100.00
Ammonium hydroxide (20%) 25.75 Effluent water 520.60 Magnesium sulfate 17.90 (Water-500,Water from
ammonium hydroxide-20.60) 0
Activated carbon 5.00 BY PRODUCT (Ammonium sulfate-19.67)
19.67
Water 500.00 Spent carbon 5.00 Organic Residue 6.38 (Process residue-6.38) Total 651.65 Total 651.65
OMEPRAZOLE SODIUM
Process Description
5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfinyl)-1H-benzoimidazole (Omeprazole) Product reacts with sodium hydroxide in the presence of Methanol to give Omeprazole sodium.
Manufacturing Process Page 170
ToR Amendment Tagoor Chemicals Private Limited
OMEPRAZOLE SODIUM Stage-1:
HN
NS
ON
O
O
(Omeprazole)
C17H19N3O3S
345.42
+ NaOH
40.00
N
OCH3
H3C CH3
SN
N OCH3O
Na
H2O
Methanol
Omeprazole SodiumC17H19N3NaO3S.H2O
385.41
5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfinyl)-
1H-benzoimidazole
Flow Chart:
OMEPRAZOLE SODIUM
Stage-1
5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfinyl)-1H-benzoimidazole (Omeprazole)Sodium hydroxideMethanol
Methanol Recovery
Material Balance:
Material Balance of Omeprazole Sodium Stage-1
Batch Size: 500.00Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfinyl)-1H-benzoimidazole (Omeprazole)
462.00 Omeprazole Sodium 500.00
Sodium hydroxide 54.00 Methanol Recovery 380.00 Methanol 400.00 Methanol Loss 10.00 Organic Residue 26.00
Manufacturing Process Page 171
ToR Amendment Tagoor Chemicals Private Limited
Process residue-16 Distillation residue-10 (Methanol-10)
Total 916.00 Total 916.00
OMEPRAZOLE
Process description:
Stage-1
3,5-Dimethyl-pyridine undergoes Oxidation with Hydrogen peroxide in presence of Acetic acid to give Stage-1 product
Stage-2
Stage-1 product undergoes Nitration with Nitric acid in presence of Sulphuric acid & Methanol to give Stage-2 product
Stage-3
Stage-2 product reacts with Dimethylsulphate in presence of Chloroform & Methanol to give Stage-3 product
Stage-4
Stage-3 product reacts with Ammonium persulphate and Ammonium sulphate in presence of Toluene & Methanol to give Stage-4 product
Stage-5
Stage-4 product undergoes Chlorination with Thionyl chloride in presence of Toluene , IPA & Acetone to give Stage-5 product
Stage-6
Stage-5 product undergoes Condensation with 2-Mercapto-5-methoxy benzimidazole in presence of Toluene, Sodium hydroxide & Water to give Stage-6 product
Stage-7
Stage-6 product undergoes Oxidation with Hydrogen peroxide in presence of Acetic acid & Dichloromethane to give Omeprazole product
Manufacturing Process Page 172
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
N
3,5-Dimethyl-pyridineC7H9N
107.15
+ H2O2
34.01
Acetic acidN+
+O-
3,5-Dimethyl-pyridine 1-oxideC7H9NO
123.15
H2O18.02
Stage-2
MethanolN+
+O-
3,5-Dimethyl-pyridine 1-oxideC7H9NO
123.15
H2O18.02
+ 2 NH3
34.06
H2SO4
98.08
+ HNO3
63.01
N+
O-
NO2
3,5-Dimethyl-4-nitro-pyridine 1-oxide
C7H8N2O3
168.15
+
Ammonium sulphate
NH4+
NH4+
S
O
O-O O-
(NH4)2SO4
132.14
+
Manufacturing Process Page 173
ToR Amendment Tagoor Chemicals Private Limited
Stage-3
Methanol, Chloroform
N+
O-
NO2
3,5-Dimethyl-4-nitro-pyridine 1-oxide
C7H8N2O3
168.15
Dimethylsulphate
SO
O
O
O+
C2H6O4S
126.13
+ 2 NaOH
80.00
+ CH3COOH
60.05
CH3OH+
32.04
N+
O
OMe
CH3SO4-
C10H17NO6S
279.31
+ CH3COONa
82.03
+ NaNO2
69.00
+ 2 H2O
36.03Methyl sulphate salt formation of 1,4-Dimethoxy-3,5-dimethyl-pyridinium
Manufacturing Process Page 174
ToR Amendment Tagoor Chemicals Private Limited
Stage-4
N+
O
OMe
CH3SO4-
C10H17NO6S
279.31 Ammonium Sulphate, Toluene & mehanol
Ammonium perSulphate,
NH4+
NH4+
O-S
O
OOOS
O
O
-O
+
1,4-Dimethoxy-3,5-dimethyl-pyridinium
methyl sulphateH8N2O8S2
228.20
N
OMe
OH
(4-Methoxy-3,5-dimethyl-pyridin-2-yl)-methanol
C9H13NO2
167.21
+
Ammonium Sulphate,
NH4+
NH4+
S
O
O
-O O-
H8N2O4S
132.14X2=264.28
+ 2 NH4OH
35.04X2=70.08
2
+ H2O2
34.02
+ CH3OH
32.02
+ 2 H2O
36.03 64.06
+ SO2 + 1.5 O2
48
Manufacturing Process Page 175
ToR Amendment Tagoor Chemicals Private Limited
Stage-5
N
O
+
C9H13NO2
167.21
OH
2-Hydroxy methyl-3,5-dimethyl-4- methoxypyridine
N
O
Cl
HCl.
C9H13Cl2NO
222.11
2-Chloromethyl-4-methoxy-3,5-dimethyl-pyridine Hydrochloride
Isopropyl alcoholToluene ,ice , Acetone ,
Sodium sulphate Activated carbon & HyflowSOCl2
118.97
+ SO2
64.06
Stage-6
C9H13Cl2NO222.11
N
O
Cl+
2-Chloromethyl-4-methoxy-3,5-dimethyl pyridine
Hydrochloride
HCl.
2-Mercapto-5-methoxy benzimidazole
N
HN
OHS
C8H8N2OS
180.23
+ 2 NaOH
80.00
Toluene & Water
N
NH
OS
NCH3
H3C OCH3
5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethylthio)-1H-benzo[d]imidazole
C17H19N3O2S329.42
+ 2 NaCl
116.89
+ 2 H2O
36.04
Manufacturing Process Page 176
ToR Amendment Tagoor Chemicals Private Limited
Stage-7
N
NH
OS
NCH3
H3C OCH3
5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethylthio)-1H-
benzo[d]imidazole
C17H19N3O2S
329.42
+
34.01
EDTA, CS Flakes , Acetic acid , Hydrose , Activated carbon, Dichloromethane
HN
NS
O
N
O
O
Omeprazole
C17H19N3O3S
345.42
+ H2O
18.01
HO OH
Manufacturing Process Page 177
ToR Amendment Tagoor Chemicals Private Limited
Flow chart:
3,5- Lutidine Hydrogen peroxide Acetic acid Sodium tungstate
Water from hydrogen peroxide+ Acetic acid Sodium tungstate Recovery
Stage-1Sulphuric acid Nitric acid (72%)Ammonia gas Methanol Water
Effluent Water
Stage-2Dimethylsulphate Sodium hydroxid flakesMethanol Acetic acidChloroform Water
Chloroform Recovery Methanol recoveryEffluent Water
Stage-3Ammonium persulphateAmmonium sulphateHydrogen peroxideMethanol Toluene Ammonium hydroxide HyflowCarbon Water
Toluene Recovery Methanol recoveryEffluent Water
Iso propyl alcohol recoveryAcetone recovery Effluent Water
Stage-4Thionyl chloride Isopropylalcohol Toluene Acetone Sodium sulphate HyflowCarbon Hydrochloric acid Liq Ammonia (15 %)Ice
Toluene RecoveryEffluent Water
Stage-1
Stage-2
Stage-3
Stage-4
Stage-5
Stage-6
Stage-52-Mercapto-5-methoxy benzimidazoleCaustic lye Toluene Water
Manufacturing Process Page 178
ToR Amendment Tagoor Chemicals Private Limited
Stage-6Hydrogen peroxide Sodium Hydroxide flakesAmmonia Acetic acid Dichloromethane HydroseActivated carbon EDTATriethylamine Water
Dichloromethane RecoveryEffluent WaterStage-7
Omeprazole
OMEPRAZOLE
Material Balance
Material Balance of Omeprazole Stage-1
Batch Size: 920Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg 3,5- Lutidine 765.00 Stage-1 878.00 Hydrogen peroxide 691.00 Water from hydrogen
peroxide+ Acetic acid 723.00
Acetic acid 145.00 Sodium tungstate Recovery
5.00
Sodium tungstate 5.00 Total 1606 Total 1606
Material Balance of Omeprazole Stage-2
Batch Size: 920Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-1 878.00 Stage-2 915.00 Sulphuric acid 3059.00 Effluent Water 1339.00 Nitric acid (72%) 1535.00 (Water-730.5Generated
water-128.5, Water from Nitric acid-430, Methanol-50)
0
Ammonia gas 1275.00 By product (Ammonium sulphate)
942.00
Methanol 50.00 Water Recovery 21000.00 Water 18000.00 Water evaporation loss 600.00 Total 24796 Total 24796
Manufacturing Process Page 179
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Omeprazole Stage-3
Batch Size: 920Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-2 915.00 Stage-3 2385.00 Dimethylsulphate 637.00 Chloroform Recovery 21000.00 Sodium hydroxid flakes 266.00 Chloroform loss 1000.00 Methanol 7000.00 Methanol recovery 6485.00 Acetic acid 80.00 Methanol loss 341.00 Chloroform 22000.00 Effluent Water 264.00 Water 4200.00 (Water-68, Generated
water-196) 0
Water recovery 2800.00 By product
(Sodium nitrite-376, Sodium acetate-447 ))
823.00
Total 35098 Total 35098
Material Balance of Omeprazole Stage-4
Batch Size: 920Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-3 2385.00 Stage-4 742.00 Ammonium persulphate 160.00 Toluene Recovery 1763.00 Ammonium sulphate 1193.00 Toluene loss 37.00 Hydrogen peroxide 581.00 Methanol recovery 6798.00 Methanol 7155.00 Methanol loss 143.00 Toluene 1855.00 Effluent Water 1543.84 Ammonium hydroxide 614.00 ( Generated water-307.65,
Methanol-273.41,Toluene-55, Water from hydrogen peroxide-907.78)
0
Hyflow 2.00 Water recovery 11500.00 Carbon 25.00 Evaporation loss 867.00 Water 12000.00 Spent Carbon & hyflow 27.00 By products
(Ammonium sulphate) 1378.30
Process emissions (sulphur dioxide-547, Oxygen-409.86)
956.86
Organic Residue Distillation Residue-214 (Methanol-214)
214.00
Total 25970 Total 25970
Manufacturing Process Page 180
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Omeprazole Stage-5
Batch Size: 920Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-4 742.00 Stage-5 715.00 Thionyl chloride 742.00 Toluene Loss 200.00 Isopropylalcohol 265.00 Iso propyl alcohol
recovery 265.00
Toluene 200.00 Acetone recovery 250.00 Acetone 250.00 Effluent Water 589.80 Sodium sulphate 50.00 (Ice-196.6,
Water from Ammonia-190, Water from Hydrochloric acid-203.2)
0
Hyflow 3.00 Water recovery 3700.00 Carbon 15.00 Spent Carbon & hyflow 18.00 Hydrochloric acid 1975.00 Inorganic solid waste
(Sodium sulphate) 50.00
Liq Ammonia (15 %) 1325.00 Process emissions (sulphur dioxide-284.30, Hydrogen chloride-494.9)
779.20
Ice 1000.00 Total 6567 Total 6567
Material Balance of Omeprazole Stage-6
Batch Size: 920Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-5 715.00 Stage-6 1000.00 2-Mercapto-5-methoxy benzimidazole
615.00 Toluene Recovery 3800.00
Caustic lye 630.00 Toluene Loss 80.00 Toluene 4000.00 Effluent Water 1431.00 Water 5000.00 (Water-500,
Generated water-116 Sodium chloride-377, Toluene-60, Water form Caustic lye-378)
0
Water recovery 4589.00 Organic Residue 60.00 Distillation Residue-60
(Toluene )
Total 10960 Total 10960
Manufacturing Process Page 181
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Omeprazole Stage-7
Batch Size: 920Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-6 1000.00 Omeprazole 920.00 Hydrogen peroxide 230.00 Dichloromethane
Recovery 2375.00
Sodium Hydroxide flakes 150.00 Dichloromethane Loss 50.00 Ammonia 4.00 Effluent Water 831.00 Acetic acid 250.00 (Water-200,
Generated water-55 Sodium hydroxide flakes-150,Ammonia-4, Acetic acid -250, Hydrose-10, Triethylamine-30, EDTA-5, Water from hydrogen peroxide-127)
0
Dichloromethane 2500.00 Water recovery 5900.00 Hydrose 10.00 Spent carbon 5.00 Activated carbon 5.00 Organic Residue 103.00 EDTA 5.00 Process residue-28
Distillation Residue-75 (Dichloromethane )
Triethylamine 30.00 Water 6000.00 Total 10184 Total 10184
OXATOMIDE
Description: Stage-1: 1- (diphenyl methyl) piperazine reacts with 1-(3-chloropropyl)1,3-dihydro-2H-
benzimidazol-2-one, in presence of Methyl Iso butyl ketone ,Soda ash, Water,
sodium hydroxide, Con HCl, to give Staeg-1 product.
Stage-2:
Stage-1 Product undergoes purification with Methanol and Carbon to give
Oxatomide.
Manufacturing Process Page 182
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis
Stage-1:
N
NH
N
HN
O
Cl
1-(3-Chloro-propyl)-1,3-dihydro-benzoimidazol-2-one
NN N
NH
O
1- (diphenyl methyl) piperazine
+
1-[3-(4-Benzhydryl-piperazin-1-yl)-propyl]-1,3-dihydro-benzoimidazol-2-one
+ NaCl
C27H30N4O
426.55
58.44
+ 1/2 Na2CO3
C17H20N2
252.35C10H11ClN2O
210.66
53.0
+ 1/2 CO2
22.0
MIBK/Sodium hydroxide
HCl
+ 1/2 H2O
9.0
Stage-2:
N NN
NH
O
1-[3-(4-Benzhydryl-piperazin-1-yl)-propyl]-1,3-dihydro-benzoimidazol-2-one
C27H30N4O
426.55
N N N
NH
O
1-[3-(4-Benzhydryl-piperazin-1-yl)-propyl]-1,3-dihydro-benzoimidazol-2-one
C27H30N4O
426.55
Methanol
Manufacturing Process Page 183
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart
Stage-1
Stage-2
1-(diphenyl methyl) piperazine1-(3-chloropropyl)1,3-dihydro-2H-benzimidazol-2-oneSodium carbonateDil. Hydrochloride MIBK
MIBK RecoveryEffluent water
Stage-1Activated CarbonMethanol
OXTOMIDE
Methanol RecoverySpent carbon
Material Balance
Material Balance of Oxtomide Stage-1
BatchSize:100 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 1-(diphenyl methyl) piperazine 65.00 Stage-1 105.00 1-(3-chloropropyl)1,3-dihydro-2H-benzimidazol-2-one
54.25 MIBK Recovery 283.00
Sodium carbonate 13.65 MIBK Loss 15.00 Dil. Hydrochloride 10.00 Effluent Water 627.32 MIBK 300.00 (Water-600,Generated wtaer-
2.28, Sodium chloride-15.04, Water from HCl-10
0
Water 600.00 Process Emission 5.65 (Carbon dioxide-5.65) 0 Organic Residue 6.93 (Process residue -4.93,
Distillation residue -2 (MIBK-2)
Total 1042.90 Total 1042.90
Material Balance of Oxtomide Stage-2
BatchSize:100 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 105.00 Oxtomide 100.00 Activated Carbon 10.00 Methanol Recovery 475.00 Methanol 500.00 Methanol Loss 10.00
Manufacturing Process Page 184
ToR Amendment Tagoor Chemicals Private Limited
Spent Carbon 10.00 Organic Residue 20.00 Process residue-5
Distillation residue-15 (Methanol-15)
Total 615.00 Total 615.00
PANTOPRAZOLE SODIUM SESQUIHYDRATE
Process description:
Stage-1
Maltol reacts with Dimethylsulphate and Sodium hydroxide in presence of Water and
Chloroform to give Stage-1 product
Stage-2
Stage-1 product reacts with Ammonium hydroxide in presence of Water to give
Stage-2 product
Stage-3
Stage-2 product reacts with Phosphorous oxychloride in presence of Ammonium
hydroxide & Water to give Stage-3 product
Stage-4
Stage-3 product reacts with Hydrogen peroxide in presence of Acetic acid,
Chloroform & Ammonium hydroxide to give Stage-4 product
Stage-5
Stage-4 product reacts with Sodium hydroxide, Methanol & Acetic anhydride in
presence of Methanol, Toluene & Chloroform to give Stage-5 product
Stage-6
Stage-5 product reacts with Sodium hydroxide in presence of Water &
Chloroform to give Stage-6 product
Stage-7
Stage-6 product undergoes Chlorination with Thionyl chloride in presence of
Methanol & Acetone to give Stage-7 product
Manufacturing Process Page 185
ToR Amendment Tagoor Chemicals Private Limited
Stage-8
Stage-7 product reacts with 5-Difluoromethoxy-2-mercapto-1H-benzimidazole in
presence of Water , Sodium hydroxide & Dichloromethane to give Stage-8 product
Stage-9
Step-A
Stage-8 product reacts with Sodium oxy chloride in presence of Acetone & Ethyl
acetate to give Step-A product
Step-B
Step-A product reacts with Sodium hydroxide in presence of Acetone & Ethyl
acetate to give Step-B product
Step-C
Step-B product reacts with Water in presence of Acetone & Ethyl acetate to give Pantoprazole Sodium Sesquihydrate product
Manufacturing Process Page 186
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
Na+
SO
O
O
-O
O
O
OH
CH3
MaltolC6H6O3
126.11
Dimethyl sulphate
(CH3)2SO4
126.13
2 NaOH
80.00
O
O
OCH3
CH3
C7H8O3
140.14
++
+
+ HCl36.46
Chloroform & water
3-Methoxy-2-methyl-pyran-4-one
+ NaCl
58.44
2 H2O+
36.03Sodium methyl sulphateCH3NaSO4
134.09
Stage-2:
O
O
OCH3
CH3
C7H8O3
140.14
+
3-Methoxy-2-methyl-pyran-4-one
NH4OH
35.05
NH
O
OCH3
CH3
3-Methoxy-2-methyl-1H-pyridin-4-one
C7H9NO2
139.15
+ 2 H2O
36.03
Manufacturing Process Page 187
ToR Amendment Tagoor Chemicals Private Limited
Stage-3
NH
O
OCH3
CH3
C7H9NO2
+ POCl3
Phosphorous oxychloride
153.33
N
Cl
OCH3
CH3
C7H8ClNO
+
3-Methoxy-2-methyl-1H-pyridin-4-one
+ 4NH4OH
4-Chloro-3-methoxy-2-methyl-pyridine
(NH4)3PO4
149
+ HCl
36.46
+
53.49
4X35.04=140.16
+ 2H2O
157.60
NH4Cl
2X18.01=36.02
139.15
Ammonium phosphate
Water
Ammonium chloride
Stage-4:
N
Cl
OCH3
CH3
C7H8ClNO
157.60
+ H2O2
Hydrogen peroxide
34.01
Chloroform , Sodium tungstate
& Methnol
N+
Cl
OCH3
CH3
O-
3-methoxy-2-methyl-4-chloro pyridine-N-oxide
C7H8ClNO173.60
+ 2 H2O
36.03
4-Chloro-3-methoxy-2-methyl-pyridine
NH4OH+
35.05
+ CH3COOH
60.05
+
Ammonium acetate
NH4+
O
-O
C2H7NO2
77.08
Manufacturing Process Page 188
ToR Amendment Tagoor Chemicals Private Limited
Stage-5:
N+
Cl
OCH3
CH3
O-
3-methoxy-2-methyl-4-chloro pyridine-N-oxide
C7H8ClNO2
173.60
NaOH
40.00
+
methanol , Chloroform , Toluene & Acetic acid+
Aceticanhydride
OO
O
C4H6O3
102.09
N
OCH3
OCH3
CH2
O
CH3
O
Acetic acid 3,4-dimethoxy-2-methylene-2H-pyridin-1-yl ester
C10H13NO4
211.21
+ CH3COOH
60.05
+ NaCl
58.44
+ CH3OH
32.04
+ H2O
18.02
Manufacturing Process Page 189
ToR Amendment Tagoor Chemicals Private Limited
STAGE-6
Activated carbon , Chloroform , Sodium sulphate & Water
+ NaOH
40.00
N
OCH3
OCH3
CH2
O
CH3
O
Acetic acid 3,4-dimethoxy-2-methylene-2H-pyridin-1-yl ester
C10H13NO4
211.21
N
OCH3
OCH3
OH
(3,4-Dimethoxy-pyridin-2-yl)-methanol
C8H11NO3
169.18
+ CH3COONa
82.03
Manufacturing Process Page 190
ToR Amendment Tagoor Chemicals Private Limited
Stage-7:
Methanol & AcetoneN
OCH3
OCH3
OH
(3,4-Dimethoxy-pyridin-2-yl)-methanol
C8H11NO3
169.18
+ SO2
64.06
+ SOCl2
118.97
N
OCH3
OCH3
Cl . HCl
2-Chloromethyl-3,4-dimethoxy-pyridine; Hydrochloride
C8H11Cl2NO2
224.08
Manufacturing Process Page 191
ToR Amendment Tagoor Chemicals Private Limited
Stage-8:
Dichloromethane & water
+N
OCH3
OCH3
Cl .HCl
2-Chloromethyl-3,4-dimethoxy-pyridine; Hydrochloride
C8H11Cl2NO2
224.08
NO
HN
F F
SH
5-Difluoromethoxy-2-mercapto-1H-benzimidazole
+
C8H6F2N2OS
216.21
2 NaOH
80.00
N
OCH3
OCH3
CH2 S
N
HN
O
F
F5-Difluoromethoxy-2-(3,4-dimethoxy-pyridin-
2-ylmethylsulfanyl)-1H-benzoimidazole
C16H15F2N3O3S
367.37
+ 2 NaCl
116.89
+ 2 H2O
36.03
Manufacturing Process Page 192
ToR Amendment Tagoor Chemicals Private Limited
Stage-9:
Step-A
Hypo , Acetone & Ethyl acetate
N
OCH3
OCH3
CH2 S
N
HN
O
F
F5-Difluoromethoxy-2-(3,4-dimethoxy-pyridin-
2-ylmethylsulfanyl)-1H-benzoimidazole
C16H15F2N3O3S
367.37
+
74.44
+ NaCl
58.44
NaOCl
N
OCH3
OCH3
CH2 S
N
HN
O
F
F
O
5-Difluoromethoxy-2-(3,4-dimethoxy-pyridin-2-ylmethanesulfinyl)-1H-benzoimidazole
C16H15F2N3O4S
383.37
Manufacturing Process Page 193
ToR Amendment Tagoor Chemicals Private Limited
Step-B
Hypo , Acetone & Ethyl acetate
+
40.00
+ H2O
18.02
NaOH
N
OCH3
OCH3
CH2 SN
HN
OF
F
O
5-Difluoromethoxy-2-(3,4-dimethoxy-pyridin-2-ylmethanesulfinyl)-1H-benzoimidazole
C16H15F2N3O4S
383.37
N
OCH3
OCH3
CH2 SN
N
O
F
F
O
Na
Pantoprazole Sodium
C16H14F2N3NaO4S
405.35
Manufacturing Process Page 194
ToR Amendment Tagoor Chemicals Private Limited
Step-C
N
OCH3
OCH3
CH2 SN
N
OF
F
O
+
Na
H2O
Pantoprazole sodium
C16H14F2N3NaO4S
405.35
27.00
Pantoprazole Sodium Sesqui Hydrate
.
C16H17F2N3NaO6S
432.37
N
OCH3
OCH3
CH2 SN
N
OF
F
O
Na
Acetone
1.5
1.5 H2O
Manufacturing Process Page 195
ToR Amendment Tagoor Chemicals Private Limited
Flow chart:
Maltol Sodium hydroxide Dimethyl sulphate Chloroform Hydrochloric acid Water
Chloroform recovery Effluent water
Stage-1Ammonium hydroxide Effluent Water
Stage-2Phosphorous oxy chloride Ammonium hydroxide Water
Effluent Water
Stage-3Hydrogen peroxide Methanol Acetic acid Ammonium hydroxideChloroform Sodium tungstate
Chloroform recovery Methanol recoveryEffluent Water
Chloroform recovery Methanol recoveryToluene recovery
Stage-4Sodium hydroxide Acetic anhydride Acetic acid Chloroform Methanol Toluene
Chloroform recovery Effluent Water
Stage-1
Stage-2
Stage-3
Stage-4
Stage-5
Stage-6
Stage-5Caustic lye Activated carbon Chloroform Sodium sulphateWater
Manufacturing Process Page 196
ToR Amendment Tagoor Chemicals Private Limited
Stage-6Thionyl chloride MethanolAcetone
Methanol Recovery Acetone recoveryStage-7
Stage-8
Stage-9
Stage-75-Difluoromethoxy-2-mercapto-1H-benzimidazoleSodium hydroxide Dichloromethane Water
Dichloromethane Recovery Effluent Water
Stage-8Sodium hypochlorite Sodium Hydroxide flakesEthyl acetate AcetoneWater
Ethyl acetate RecoveryAcetone RecoveryEffluent Water
Pantoprazole Sodium Sesquihydrtae
PANTOPRAZOLE SODIUM SESQUIHYDRATE
Material balance
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-1
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Maltol 557.00 Stage-1 557.00 Sodium hydroxide 483.00 Chloroform recovery 2660.00 Dimethyl sulphate 669.00 Chloroform loss 140.00 Chloroform 2800.00 Effluent water
(Water -268 generated water-163, Sodium chloride-258.1)
689.10
Hydrochloric acid 33.00 Water recovery 2182.00 Water 2450.00 By product
(Sodium methyl sulphate-711)
711.00
Organic residue 52.90 Total 6992 Total 6992
Manufacturing Process Page 197
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-2
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-1 557.00 Stage-2 557.00 Ammonium hydroxide 836.00 Effluent water
(generated water-143.20Watre from ammonium hydroxide-692.8)
836.00
Total 1393 Total 1393
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-3
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-2 557.00 Stage-3 537.00 Phosphorous oxy chloride 896.00 Effluent water
(generated water-144.18,Water from Ammonium hydroxide-530.68)
674.86
Ammonium hydroxide 1592.00 Water recovery 3840.00 Water 3342.00 By product
(Ammonium Phosphate-870 Ammonium chloride -312.20)
1189.20
Process emission (Hydrogen chloride)
145.94
Total 6387 Total 6387
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-4
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-3 537.00 Stage-4 557.00 Hydrogen peroxide 583.00 Chloroform recovery 2645.00 Methanol 567.00 Chloroform loss 140.00 Acetic acid 58.00 Methanol recovery 539.00 Ammonium hydroxide 179.00 Methanol loss 11.00 Chloroform 2785.00 Effluent water
(generated water-123, Sodium tungstate-18, Water from hydrogen
555.00
Manufacturing Process Page 198
ToR Amendment Tagoor Chemicals Private Limited
peroxide-414) Sodium tungstate 18.00 By product
(Ammonium acetate ) 263.00
Organic residue Distillation Residue-17 (Methanol)
17.00
Total 4727 Total 4727
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-5
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-4 557.00 Stage-5 557.00 Sodium hydroxide 140.00 Chloroform recovery 346.00 Acetic anhydride 335.00 Chloroform loss 18.00 Acetic acid 220.00 Methanol recovery 1226.00 Chloroform 364.00 Methanol loss 28.00 Methanol 1393.00 Toluene recovery 133.00 Toluene 140.00 Toluene loss 7.00 By product
(Acetic acid -569,) 569.00
Effluent water (Generated water -57.81, Sodium chloride-145)
202.81
Organic residue Process residue-26.19 Distillation Residue-36 (Methanol)
62.19
Total 3149 Total 3149
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-6
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-5 557.00 Stage-6 429.00 Caustic lye 995.00 Chloroform recovery 3838.00 Activated carbon 15.00 Chloroform loss 202.00 Chloroform 4040.00 Effluent water
(Water from Sodium hydroxide-875)
875.00
Sodium sulphate 30.00 Water recovery 3180.00 Water 3180.00 By product
(Sodium acetate) 248.00
Spent carbon 15.00
Manufacturing Process Page 199
ToR Amendment Tagoor Chemicals Private Limited
Inorganic solid waste (Sodium sulphate)
30.00
Total 8817 Total 8817
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-7
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-6 429.00 Stage-7 500.00 Thionyl chloride 378.00 Methanol Recovery 713.00 Methanol 750.00 Methanol loss 15.00 Acetone 1275.00 Acetone recovery 1211.00 Acetone loss 26.00 Process emission
(sulphur dioxide-162.44) 162.44
Organic Residue 204.56 Process residue-144.56
Distillation Residue-60 (Methanol-22, Acetone-38)
Total 2832 Total 2832
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-8
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-7 500.00 Stage-8 825.00 5-Difluoromethoxy-2-mercapto-1H-benzimidazole
500.00 Dichloromethane Recovery
4750.00
Sodium hydroxide 225.00 Dichloromethane loss 100.00 Dichloromethane 5000.00 Effluent Water 5400.00 Water 5000.00 (Water-5000
Generated water-80.39 , Sodium chloride-319.61)
0
Organic Residue 150.00 Distillation Residue-150
(Dichloromethane)
Total 11225 Total 11225
Manufacturing Process Page 200
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Pantoprazole Sodium Sesquihydrtae Stage-9
Batch Size: 750Kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-8 825.00 Pantoprazole Sodium
Sesquihydrtae 750.00
Sodium hypochlorite 7500.00 Ethyl acetate Recovery 1900.00 Sodium Hydroxide flakes 80.00 Ethyl acetate Loss 40.00 Ethyl acetate 2000.00 Acetone Recovery 3800.00 Acetone 4000.00 Acetone Loss 80.00 Water 5000.00 Effluent Water 1715.00 (Water-1169, Generated
water-40.46 , Ethyl acetate-60, Sodium chloride-445.54)
0
Water recovery 11000.00 Organic Residue 120.00 Distillation Residue-120
(Acetone-120)
Total 19405 Total 19405
PIMOZIDE
Process Description:
Stage-1:
4-chloro-1, 1-bis (4-fluorophenyl) butane (PIM-III) react with 1-(piperidin-4-yl) 1H-benza
imidazole-2(3H)-one (Keto-9) in presence of sodium carbonate, tetrabutyl ammonium
bromide, MIBK to give Stage-1 product
Stage-2:
Stage-1 Product undergoes Purification with Methanol and carbon to form Pimozide.
Manufacturing Process Page 201
ToR Amendment Tagoor Chemicals Private Limited
Route of synthesis
Stage-1
F
F
N
HN
O
NH
F
F
NHN
ON
Cl
4-chloro-1,1-bis(4-fluorophenyl)butane
1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
1-(1-(4,4-bis(4-fluorophenyl)butyl)piperidin-4-yl)-1H-
benzo[d]imidazol-2(3H)-one
+ + 1/2 Na2CO3
MIBK
TBAB
53.0
+ NaCl + 1/2 H2O + 1/2 CO2
58.44 9.0 22.0
C16H15ClF2
280.74C12H15N3O
217.27
C28H29F2N3O
461.55
Manufacturing Process Page 202
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
F
F
NHN
ON
1-(1-(4,4-bis(4-fluorophenyl)butyl)piperidin-4-yl)-1H-benzo
[d]imidazol-2(3H)-one
F
F
NHN
ON
Pimozide
(Pimozide Crude)
Methanol
Activated Carbon
C28H29F2N3O
461.55
C28H29F2N3O
461.55
Flow Chart
Stage-1
Stage-2
PIMOZIDE
4-chloro-1, 1-bis (4-fluorophenyl) butane (PIM-III) 1-(piperidin-4-yl) 1H-benza imidazole-2(3H)-one (Keto-9)Sodium carbonate (25%)Potassium IodideTetra butyl ammonium bromideMIBK
MIBKl RecoveryEffluent water
Stage-1Activated CarbonMethanol
Methanol recoverySpent carbon
Manufacturing Process Page 203
ToR Amendment Tagoor Chemicals Private Limited
Material Balance
Material Balance of Pimozide Stage-1
BatchSize:100 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 4-chloro-1, 1-bis (4-fluorophenyl) butane (PIM-III)
67.00 Stage-1 105.00
1-(piperidin-4-yl) 1H-benza imidazole-2(3H)-one (Keto-9)
52.00 MIBK Recovery 285.00
Sodium carbonate (25%) 50.00 MIBK Loss 12.00 Potassium Iodide 1.00 Effluent Water 457.09 Tetra butyl ammonium bromide 2.50 (Water-400,Generated water-
2.14,water form Sodium carbonate-37.5,Sodium Chloride-13.95, Potassium Iodide-1,TBAB-2.5)
MIBK 300.00 Process Emission 5.22 Water 400.00 (Carbon dioxide-5.22) Organic Residue 8.19 (Process residue -5.19,
Distillation residue-3 MIBK-3)
Total 872.50 Total 872.50
Material Balance of Pimozide Stage-2
BatchSize:100 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 105.00 Pimozide 100.00 Activated Carbon 5.00 Methanol Recovery 285.00 Methanol 300.00 Methanol Loss 10.00 Spent Carbon 5.00 Organic Residue 10.00 Process residue-5
Distillation residue -5 Methanol-5
Total 410.00 Total 410.00
Manufacturing Process Page 204
ToR Amendment Tagoor Chemicals Private Limited
PREGABALIN
Process Description:
Stage-1
2-(1-Cyano-3-methyl-butyl)-malonic acid diethyl ester reacts with Hydrogen in
presence of Raney Nickel, Potassium hydroxide, Acetic acid and Water to give
Stage-1 product.
Stage-2
Stage-1 product reacts with Mandelic acid in presence of IPA to give Stage-2
product.
Stage-3
Stage-2 product reacts with Sodium hydroxide in presence of THF to give Pregabalin
product.
Manufacturing Process Page 205
ToR Amendment Tagoor Chemicals Private Limited
PREGABALIN
Route of Synthesis:
Stage –1
2-(1-Cyano-3-methyl-butyl)-malonic acid diethyl ester
C13H21NO4
255.31
CH3C
CH3
N
O
OC2H5
C
O
OC2H5
KOH + CH3COOH
CH3COOK CO22 C2H5OH
+
+++
56.11 60.05
C8H17NO2
159.23
98.14 44.003-Aminomethyl 5 -methyl
hexanoic acid
H2O
18.00
Raney Nickel
+ 2H2
2X2=4.0
+
H3C
H3C
NH2
COOH
2 X46.07=92.14
Methanol
Manufacturing Process Page 206
ToR Amendment Tagoor Chemicals Private Limited
Stage –2
C8H17NO2
2 x 159.23 = 318.46
3-Aminomethyl 5 -methylhexanoic acid
H3C
H3CNH2
COOH
+ COOH
OH
Mandelic acidC8H8O3
152.15
IPA
-OOC
HO
C16H25NO5
S(+)Pregabalin mandalate salt
H3C
H3CNH3
+
COOH
+ (R)-Isomer
159.23
2
311.37
Stage –3
-OOC
HO
C16H25NO5
311.37
S(+)Pregabalin mandalate salt
H3C
H3C
NH3+
COOH
COOH
OH
Mandelic acid
C8H8O3
152.14
C8H17NO2
159.23
S(+)Pregabalin
THF
H3C
H3C
NH2
COOH
+NaOH
Manufacturing Process Page 207
ToR Amendment Tagoor Chemicals Private Limited
PREGABALIN
Flow Chart:
2-(1-Cyano-3-methyl-butyl)-malonic acid diethyl esterEthanolPotassium hydroxideAcetic acidRaney nickelIPAHydrogen gas
Ethanol Recovery IPA Recovery
stage-1
IPA Recoverystage-2
THF Recovery IPA Recovery
stage-3
Stage-1(S)-Mandelic acidIsopropyl alcohol
Stage -2TetrahydrofuranIsopropyl alcohol
Pregabalin
Manufacturing Process Page 208
ToR Amendment Tagoor Chemicals Private Limited
PREGABALIN Material Balance:
Material Balance Of Pregabalin Stage-1
Batch Size: 200.0Kgs Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 2-(1-Cyano-3-methyl-butyl)-malonic acid diethyl ester
753.00 Stage-1 445.00
Ethanol 200.00 Ethanol Recovery 461.08 Potassium hydroxide 165.00 Ethanol loss 10.00 Acetic acid 176.95 IPA Recovery 333.00 Raney nickel 5.00 IPA Loss 12.00 IPA 350.00 Raney Nickel Reuse 5.00 Hydrogen gas 11.30 Effluent water 836.44 Water 600.00 (Water-547.29,Poatassium
acetate-289.15)
Process emission 129.52 (Carbon dioxide-129.52) 0 Organic residue 29.21 Process residue-24.21
Distillation residue-5 (IPA-5)
Total 2261.25 Total 2261.25
Material Balance Of Pregabalin Stage-2
Batch Size: 200.0Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 445.00 Stage -2 413.00 (S)-Mandelic acid 213.00 IPA Recovery 475.00 Isopropyl alcohol 500.00 IPA Loss 10.00 Water 300.00 Effluent water 300.00 (Water-300) Organic residue 260.00 Process residue-
245,organic impurities-22.5 (R-Isomer Recycle-222.5) Distillation residue-15 (IPA-15)
Total 1458.00 Total 1458.00
Manufacturing Process Page 209
ToR Amendment Tagoor Chemicals Private Limited
Material Balance Of Pregabalin Stage-3
Batch Size:200.0Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage -2 413.00 Pregabalin 200.00 Tetrahydrofuran 300.00 THF Recovery 285.00 Isopropyl alcohol 400.00 THF Loss 15.00 Sodium Hydroxide 5.00 IPA Recovery 385.00 Water 500.00 IPA Loss 15.00 Effluent water 505.00 (Water-500,Sodium
hydroxide-5) 0
Organic residue 213.00 Process residue-213
(Organic impurities-11.46 Mandelic acid recovery-201.54) Distillation residue-5 (IPA-5)
Total 1618.00 Total 1618.00
QUETIAPINE FUMARATE
Process Description:
Stage-1:
11-Piperazin-1-yl-4a,11a-dihydro-dibenzo[b,f] [1,4]thiazepine Di hydrochloride reacts with 2-Chloroethoxy ethanol in presence of Sodium carbonate, Toluene and water to give Stage-1 product.
Stage-2:
Stage-1 product reacts with Fumaric acid in presence of Acetone to give Quetiapine Fumarate.
Manufacturing Process Page 210
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
S
NN
NH . 2 HCl
11-Piperazin-1-yl-4a,11a-dihydro-dibenzo[b,f][1,4]thiazepine Di hydrochloride
C17H21Cl2N3S
370.34
+
2-Chloroethoxy ethanol
HOO
Cl
C4H9ClO2
124.57
+ Na2CO3
105.99
S
NN
NO
OH
2-{2-[1-(4a,11a-Dihydro-dibenzo[b,f][1,4]thiazepin-11-yl)-piperidin-4-yl]-ethoxy}-ethanol(Quetiapine)
C21H27N3O2S
385.52
+ 2 NaCl
116.89
+ CO2
44.01
+ H2O
18.02
+ HCl
36.46
Toluene
Stage-2
S
NN
NO
OH
2-{2-[1-(4a,11a-Dihydro-dibenzo[b,f][1,4]thiazepin-11-yl)-piperidin-4-yl]-ethoxy}-
ethanol(Quetiapine)
C21H27N3O2S
771.00
+
Fumaric acid
O
OHO
HO
C4H4O4116.07
2
S
NN
NO
OH
2.
O
OHO
HO
Quetiapine Fumarate
C46H58N6O8S2
887.12
Acetone
Manufacturing Process Page 211
ToR Amendment Tagoor Chemicals Private Limited
Flowchart:
Stage-1
Stage-2
11-Piperazin-1-yl-4a,11a-dihydro-dibenzo[b,f][1,4]thiazepine Dihydrochloride2-Chloroethoxy ethanolSodium carbonateToluene
Toluene recoveryEffluent water
Stage-1Fumaric acidAcetone
Acetone RecoveryEffluent water
QUETIAPINE FUMARATE
Material Balance:
Material Balance of Quetiapine Fumarate. Stage-1
Batch Size: 100.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg 11-Piperazin-1-yl-4a,11a-dihydro-dibenzo[b,f] [1,4]thiazepine Di hydrochloride
90.00 Stage-1 90.00
2-Chloroethoxy ethanol 30.25 Toluene Recovery 285.00 Sodium carbonate 25.75 Toluene loss 10.00 Toluene 300.00 Effluent water 434.59 Water 400.00 (Water-400, Generated water –
4.32, Sodium chloride-27.27,Toluene-3)
Process emission 19.44 (Hydrogen Chloride– 8.82,
Carbon dioxide-10.62)
Organic residue 6.97 Process residue – 4.97
Distillation residue-2 ((Toluene-2)
Total 846.00 Total 846.00
Manufacturing Process Page 212
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Quetiapine Fumarate. Stage-2
Batch Size: 100.00 Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 90.00 Quetiapine Fumarate. 100.00 Fumaric acid 13.50 Acetone Recovery 285.00 Acetone 300.00 Acetone loss 10.00 Water 400.00 Effluent water 400.00 (Water-400) 0 Organic residue 8.50 Process residue – 3.50
Distillation residue-5 (Acetone-5)
Total 803.50 Total 803.50
RABEPRAZOLE SODIUM
Process Description
Stage-1
2, 3-Lutidine reacts with Hydrogen Peroxide and Nitric acid in presence of Sulfuric Acid and water to give Stage-1Product.
Stage-2
Stage-1 Product reacts with 3-Methoxy-1-Propanol and Sodium Hydroxide in presence of Toluene and DMSO to give Stage-2 Product.
Stage-3
Stage-2 Product reacts with Acetic Anhydride in presence of Sodium Hydroxide, Toluene and Hydrochloric Acid to give Stage-3 Product.
Stage-4
Stage-3 Product reacts with Thionyl Chloride in the presence of Toluene,Methanol and MDC to giveStage-4 Product.
Manufacturing Process Page 213
ToR Amendment Tagoor Chemicals Private Limited
Stage-5
Stage-4 Product reacts with 2-Mercapto Benzimidazole, in presence of Toluene, methanol to give Stage-5 Product.
Stage-6
Stage-5 Product reacts with Sodium Hypochlorite in presence of MDC and Toluene to give Stage-6 product.
Stage-7
Stage-6 product reacts with Sodium hydroxide in presence of Acetone to get Rabeprazole Sodium
Route of Synthesis:
Stage-1
N
CH3
CH3
2,3-LutidineC7H9N107.15
+ H2O2
34.01
+ HNO3
63.0
H2SO4+ 2H2O
36.0
C7H8N2O3
168.15
N+
O-
H3C
H3C
NO2
2,3-Dimethyl-4-nitro-pyridine 1-oxide
Manufacturing Process Page 214
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
C7H8N2O3
168.15
4-Nitro-2,3-Dimethyl pyridine-N-oxide
3-Methoxy-1-Propanol
HO O + NaOH+
C4H10O2
90.12
C11H17NO3
211.26
+ NaNO2 + H2O
Sodium Nitrite
69.0
18.0
40.0
N+
O-
H3C
H3C
NO2
N+
H3C
O O
O-
H3C
4-(3-Methoxy-propoxy)-2,3-dimethyl-pyridine 1-oxide
Toluene
DMSO
Stage-3
C11H17NO3
211.26
N+
H3C
O O
O-
H3C
4-(3-Methoxy-propoxy)-2,3-dimethyl-pyridine 1-oxide
OO
O
+
Acetic anhydride
NaOH
4(3-methoxy propoxy)-2-hydroxy methyl -3-methyl pyridine hydrochloride
+
CH3COONa+ CH3COOH
82.0 60.0
40.0
C11H17NO3 HCl
247.72
+ HCl
36.5C4H6O3
102.09
HClN
OH
OO
.+
Toluene
Methanol
Manufacturing Process Page 215
ToR Amendment Tagoor Chemicals Private Limited
Stage-4
Toluene
Methanol
4(3-methoxy propoxy)-2-hydroxy methyl -3-methyl pyridine hydrochloride
+
C11H17NO3 HCl
247.72
HClN
OH
OO
. SOCl2
118.97
Thionyl Chloride 2-(chloromethyl)-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride
HClN
Cl
OO
.
C11H17Cl2NO2
266.16
SO2+ HCl
64.0 36.46
+
Stage-5
Toluene
Methanol
2-(chloromethyl)-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride
HClN
Cl
OO
.
C11H17Cl2NO2
266.16
2-Mercapto benzimidazole
N
HN
HS +
80.00
2 NaOH
C7H6N2S
150.25
+
2-[4-(3-Methoxy-propoxy)-3-methyl-pyridin-2-ylmethylthio]-1H-benzo[d]imidazole
NCH2
O O
N
NH
S
C18H21N3O2S
343.44
+ + 2 H2O
36.03
2 NaCl
116.89
Manufacturing Process Page 216
ToR Amendment Tagoor Chemicals Private Limited
Stage-6
2-[4-(3-Methoxy-propoxy)-3-methyl-pyridin-2-ylmethylthio]-1H-benzo[d]imidazole
NCH2
O O
N
NH
S
C18H21N3O2S343.44
+ NaOCl
NCH2
O O
N
NH
S
O
2-[4-(3-Methoxy-propoxy)-3-methyl-pyridin-2-ylmethanesulfinyl]-1H-benzoimidazole
C18H21N3O3S
359.44
+ NaCl
58.5
74.44
Sodium Hypochlorite
Toluene
MDC
Stage-7
NCH2
O O
N
NH
S
O
2-[4-(3-Methoxy-propoxy)-3-methyl-pyridin-2-ylmethanesulfinyl]-1H-benzoimidazole
C18H21N3O3S
359.44
+ NaOH NCH
O O
N
NH
S
O
Na
Rabeprazole Sodium40.0 + H2O
18.0C18H20N3NaO3S
381.42
Acetone
Manufacturing Process Page 217
ToR Amendment Tagoor Chemicals Private Limited
RABEPRAZOLE SODIUM
Flow Chart:
Stage-1
Stage-2
Stage-3
Stage-4
Stage-5
Stage-6
Stage-7
2,3-LutidineHydrogen Peroxide (50%)Nitric acidSulphuric acidAcetic acid
Effluent water
Stage-13-Methoxy-1-PropanolSodium HydroxideTolueneDMSO
Toluene RecoveryDMSO RecoveryGenerated water
Stage-2Acetic anhydrideSodium HydroxideHydrochloric acidTolueneMethanol
Toluene RecoveryMthanol RecoveryEffluent water
Stage-3Thionyl ChlorideMDCSodium SulphateToluene Methanol
Methanol RecoveryMDC RecoveryEffluent water
Stage-42-MercaptobenzimidazoleSodium hydroxideTolueneMethanol
Toluene RecoveryMethanol RecoveryEffluent water
Stage-5Sodium Hypochlorite (8%)MDCToluene Sodium hydro sulphateMMA in Methanol
MDC RecoveryEffluent water
Stage-6Sodium HydroxideAcetone Activated Carbon
Acetone Recovery Generated water
RABEPRAZOLE SODIUM
Manufacturing Process Page 218
ToR Amendment Tagoor Chemicals Private Limited
RABEPRAZOLE SODIUM
Material Balance:
Material balance of Rabeprazole Sodium Stage-1 Batch Size: 500Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
2,3-Lutidine 210.00 Stage-1 310.00 Hydrogen Peroxide (50%) 135.00 Spent Acids for sale 140.00 Nitric acid 124.00 (Sulfuric Acid-100,Acetic
Acid-40)
Sulphuric acid 108.00 Effluent Water 552.55 Acetic acid 46.00 (Water-400,Sulfuric Acid-
8,Acetic Acid-6,Generated water-70.55,Water from Hydrogen peroxide-68)
Water 400.00 Organic Residue 20.45 Process resiue-20.45 Total 1023.00 Total 1023.00
Material balance of Rabeprazole Sodium Stage-2 Batch Size: 500Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-1 310.00 Stage-2 370.00 3-Methoxy-1-Propanol 167.00 Toluene Recovery 235.00 Sodium Hydroxide 74.00 Toluene Loss 12.00 Toluene 250.00 DMSO Recovery 188.00 DMSO 200.00 DMSO Loss 10.00 Generated water 33.18 Inorganic Solid Waste 127.20 (Sodium Nitrite-127.20) 0 Organic residue 25.62
Process residue-20.62 Distillation residue-5 (Toluene-3,DMSO-2)
Total 1001.00 Total 1001.00
Material balance of Rabeprazole Sodium Stage-3 Batch Size: 500Kg
Name of the input Quantity in Kg
Name of the out put Quantity in Kg
Stage-2 370.00 Stage-3 412.00 Acetic anhydride 179.00 Toluene Recovery 380.00 Sodium Hydroxide 70.00 Toluene Loss 10.00
Manufacturing Process Page 219
ToR Amendment Tagoor Chemicals Private Limited
Hydrochloric acid 64.00 Methanol Recovery 475.00 Toluene 400.00 Methanol Loss 15.00 Methanol 500.00 Effluent Water 510.00 Water 400.00 (Water-400 ,Acetic
Acid-105, Toluene-5) 0.00
By product (Sodium Acetate-143.61)
143.61
Organic Residue 37.39 Process residue-22.39
Distillation residue-15 (Toluene-5,Methanol-10)
Total 1983.00 Total 1983.00
Material balance of Rabeprazole Sodium Stage-4
Batch Size: 500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 412.00 Stage-4 420.00 Thionyl Chloride 198.00 MDC Recovery 710.00 MDC 750.00 MDC Loss 37.00 Sodium Sulphate 10.00 Toluene Recovery 475.00 Toluene 500.00 Toluene Loss 10.00 Methanol 500.00 Methanol Recovery 475.00 Water 500.00 Methanol Loss 15.00 Effluent Water 508.00 (Water-500,Toluene-8) 0 Inorganic Solid Waste 10.00 (Sodium Sulphate) 0 Process Emission 167.08 (sulfur dioxide-106.44,
Hydrogen chloride-60.64)
0
Organic Residue 42.92 Process residue -22.92
Distillation residue-20 (Methanol-10, Toluene-7, MDC-3)
Total 2870.00 Total 2870.00
Manufacturing Process Page 220
ToR Amendment Tagoor Chemicals Private Limited
Material balance of Rabeprazole Sodium Stage-5
Batch Size: 500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-4 420.00 Stage-5 510.00 2-Mercaptobenzimidazole 240.00 Toluene Recovery 380.00 Sodium hydroxide 127.00 Toluene Loss 10.00 Toluene 400.00 Methanol Recovery 380.00 Methanol 400.00 Methanol Loss 10.00 Water 400.00 Effluent Water 646.31 (Water-400,Sodium
chloride-184.45,Generated water-56.86,Toluene-5)
0
Organic Residue 50.69 Process residue-35.69,
Distillation residue-15 (Toluene-5, Methanol-10)
Total 1987.00 Total 1987.00
Material balance of Rabeprazole Sodium Stage-6
Batch Size: 500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-5 510.00 Stage-6 500.00 Sodium Hypochlorite (8%) 1388.00 MDC Recovery 570.00 MDC 600.00 MDC Loss 30.00 Toluene 150.00 Toluene Recovery 143.00 Sodium hydro sulphate 12.00 Toluene Loss 5.00 MMA in Methanol 10.00 Effluent Water 1775.87 Water 400.00 (Water-400,Sodium
Chloride-86.87,water from sodium hypochlorite-1277, ,MMA-10, Toluene-2)
Organic Solid Waste 46.13 Process residue-43.13
Distillation residue-3 (Toluene-3)
Total 3070.00 Total 3070.00
Manufacturing Process Page 221
ToR Amendment Tagoor Chemicals Private Limited
Material balance of Rabeprazole Sodium Stage-7
Batch Size: 500Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-6 500.00 Rabeprazole Sodium 500.00 Sodium Hydroxide 56.00 Acetone Recovery 280.00 Acetone 300.00 Acetone Loss 15.00 Activated Carbon 10.00 Generated water 25.00 Spent carbon 10.00 Organic Residue 36.00 (Process residue-31,
Distillation residue-5 (Acetone-5)
Total 866.00 Total 866.00
RUPATADINE FUMERATE
Process Description: Stage-1:
8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo(5,6)cyclohepta(1,2-b)pyridine react with 3-chloromethyl-5-methylpyridine in presence of sodium hydroxide, water, TBAB, Ethyl acetate to give stage-1 product. Stage-2 : Stage-1 product reacts with But-2-enedioic acid in presence of Methanol, Acetone to give Rupatadine Fumerate Route of synthesis Stage-1
N
NH
Cl
N
Cl
N
N
Cl
N
3-(chloromethyl)-5-methylpyridine
8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5H-benzo
[5,6]cyclohepta[1,2-b]pyridine
Sodium hydroxide,TBAB
8-Chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
Ethyl acetate
+
C19H19ClN2
310.82
C7H8ClN
141.6 C26H26ClN3
415.96
Manufacturing Process Page 222
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
N
N
Cl
N
8-Chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine N
N
Cl
N
8-Chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinylidene]-
5H-benzo[5,6]cyclohepta[1,2-b]pyridine fumeric acid
COOHH
HOOC H
Methanol,AcetoneCOOHH
HOOC H
+
But-2-enedioic acid
C4H4O4
116.07C26H26ClN3
415.96
C30H30ClN3O4
532.03
Flow Chart
Stage-1
Stage-2
8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo(5,6)cyclohepta(1,2-b)pyridine3-chloromethyl-5-methylpyridineEthyl acetateSodium hydroxideTBAB
Ethyl acetate RecoveryEffluent water
Stage-1But-2-enedioic acidMethanolAcetoneActivated carbon
Methanol recoveryAcetone recovery
RUPATADINE FUMERATE
Manufacturing Process Page 223
ToR Amendment Tagoor Chemicals Private Limited
RUPATADINE FUMERATE
Material Balance
Material Balance of Rupatadine Fumerate Stage-1
BatchSize:100.0Kg Name of the input Quantity in
Kg Name of the out put Quantity in
Kg 8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo(5,6)cyclohepta(1,2-b)pyridine(DLRD)
62.00 Stage-1 80.00
3-chloromethyl-5-methylpyridine 28.20 Ethyl acetate Recovery 190.00
Ethyl acetate 200.00 Ethyl acetate Loss 5.00 Sodium hydroxide 20.00 Effluent water 625.00 TBAB 2.00 (Water-600,TBAB-2,
Sodium hydroxide-20, Ethyl acetate-3)
0
Water 600.00 Organic Residue 12.20 Process residue-10.20
Distillation residue-2 (Ethyl acetate-2)
Total 912.20 Total 912.20
Material Balance of Rupatadine Fumerate Stage-2
BatchSize:100.0Kg Name of the input Quantity
in Kg Name of the out put Quantity in
Kg Stage-1 80.00 Rupatadine Fumerate 100.0 But-2-enedioic acid 22.30 Acetone Recovery 93.00 Methanol 150.00 Acetone Loss 5.00 Acetone 100.00 Methanol Recovery 143.00 Activated carbon 5.00 Methanol Loss 4.00 Spent carbon 5.00 Organic residue 7.30
Process residue-2.30 Distillation residue-5 ( Acetone-2,Methanol-3)
Total 357.30 Total 357.30
TELMISARTAN
Manufacturing Process Page 224
ToR Amendment Tagoor Chemicals Private Limited
Process Description
Stage-1
4-Methyl-biphenyl-2-carbonitrile undergoes hydrolysis with Potassium Hydroxide
inpresence of Ethylene glycol and HCl to give Stage-1 product. Stage-2
Step-A
Stage-1product undergoes methylation with Dimethyl sulphate in presence of
Potassium carbonate and MDC to give step-A product.
Step-B Step-A product undergoes Bromination with DDH in presence of Acetone and Cyclo
hexane to give Stage-2 product.
Stage-3
Stage-2 product undergoes condensation with 1,7’-Dimethyl-2’-propyl-
3’a,4’,5’,6’,7’,7’,a-hexahydro-1H,3’H-[2,5’]bibenzoimidazolyl in presence of
potassium hydroxide and acetone to give stage-3 product..
Stage-4
Stage-3 product undergoes hydrolysis with Potassium Hydroxide in presence of
water and Acetic acid to give Telmisartan.
Manufacturing Process Page 225
ToR Amendment Tagoor Chemicals Private Limited
Route of Synthesis:
Stage-1
+ HO OHEthylene glycol
CH3
CN
4'-Methyl-biphenyl-2-carbonitrile
+KOH
CH3
COOH
+ + NH3
56.11
+ HCl
KCl +
C14H11N
193.24
C2H6O2
62.07
36.46
4'-Methyl-biphenyl-2-carboxylic acid
C14H12O2
212.24
74.55 17.03
+ H2O
18.02
CH3COOH
60.05+ H2
2.02
Manufacturing Process Page 226
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
Step-A
CH3
COOH
4'-Methyl-biphenyl-2-carboxylic acid
C14H12O2
212.24
+
Dimethyl sulphate
126.13
+ K2CO3
138.21
CH3
COOCH3
+ CH3OH + K2SO4 + CO2
44.00
C2H6SO4
4'-Methyl-biphenyl-2-carboxylic acid methyl ester
C15H14O2
226.27
32.04 174.26
Manufacturing Process Page 227
ToR Amendment Tagoor Chemicals Private Limited
Step-B
CH3
COOCH3
4'-Methyl-biphenyl-2-carboxylic acid methyl ester
C15H14O2
226.27
NON
OCH3CH3
Br
Br
DibromodimethylHydantoin
H2C
COOCH3
Br
+NO
N
O
CH3
CH3
Br
H
1-Bromo-5,5-dimethyl-imidazolidine-2,4-dione
+
C5H6Br2N2O2
285.92
C15H13O2Br
305.17
4'-Bromomethyl-biphenyl-2-carboxylic acid methyl ester
C5H7BrN2O2
207.03
Manufacturing Process Page 228
ToR Amendment Tagoor Chemicals Private Limited
Stage-3
H2C
COOCH3
Br
+
C15H13O2Br
305.17
4'-Bromomethyl-biphenyl-2-carboxylic acid methyl ester
+ KOH
COOCH3N N
H3C N
N
CH3
CH3
+
Telmisartan Ester
N N
H3C NNH
CH3
CH3
310.44
C19H26N4
1,7'-Dimethyl-2'-propyl-3'a,4',5',6',7',7'a-hexahydro-1H,
3'H-[2,5']bibenzoimidazolyl
56.11
C34H32N4O2
534.69
KBr H2O+
119 18.02
Manufacturing Process Page 229
ToR Amendment Tagoor Chemicals Private Limited
Stage-4
COOCH3N N
H3C NN
CH3
CH3
+
Telmisartan EsterC34H32N4O2
534.69
+ KOH + CH3COOHWater
MDCCOOH
N N
H3C NN
CH3
CH3
Telmisartan
CH3OH + CH3COOK
56.11 60.05
520.66
C33H36N4O2
32.04 Potassium Acetate
98.14
Manufacturing Process Page 230
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart:
Stage-1
Stage-2
Stage-3
Stage-4
TELMISARTAN
4-methyl-biphenyl-2-carbonitrileEthylene glycolPotassium HydroxideHydrochloric acid
Effluent water
Stage-1Di methyl sulphateDibromodimethyl HydantoinPotassium CarbonateAcetoneCyclohexaneActivated CarbonMDC
Acetone RecoveryMDC recoveryEffluent water
Stage-21,7'-Dimethyl-2'-propyl-3'a,4',5',6',7',7'a-hexahydro-1H,3'H-[2,5']bibenzoimidazolylPotassium HydroxideAcetone
Acetone RecoveryEffluent water
Stage-3Potassium HydroxideAcetic acidDMFMethanolMDCActivated Carbon
MDC RecoveryMethanol RecoveryEffluent water
Manufacturing Process Page 231
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material, balance of Telmisartan Stage-1
Batch Size:100kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg 4-methyl-biphenyl-2-carbonitrile
52.00 Stage-1 53.00
Ethylene glycol 16.70 Effluent Water 631.31 Potassium Hydroxide 15.08 (Water-595.17,
Potassium chloride-20.02, Acetic acid-16.12)
0
Hydrochloric acid 9.77 Process Emission 5.09 Water 600.00 (Ammonia-4.57,Hydrogen-
0.52)
Organic Residue 4.15 Process Residue-4.15 Total 693.55 Total 693.55
Material, balance of Telmisartan Stage-2
Batch Size:100kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-1 53.00 Stage-2 67.00 Di methyl sulphate 31.50 MDC Recovery 570.00 Dibromodimethyl Hydantoin 66.95 MDC Loss 12.00 Potassium Carbonate 34.50 Acetone Recovery+ Methanol 387.95 Acetone 400.00 Acetone Loss 10.00 Cyclohexane 200.00 Cyclohexane Recovery 190.00 Activated Carbon 5.00 Cyclohexane Loss 5.00 MDC 600.00 Effluent Water 843.50 Water 800.00 (Water-800,Potassium
sulphate-43.50) 0
Spent Carbon 5.00 Process Emission 10.98 (Carbon dioxide-10.98) 0 Organic Residue 89.52 Process Residue-56.52
Organic impurities-8.08 (1-Bromo-5,5-dimethyl-imidazolidine-2,4-dione-48.44) Distillation Residue-33 (Acetone-10,Cyclo hexane-5,MDC-18)
Total 2190.95 Total 2190.95
Manufacturing Process Page 232
ToR Amendment Tagoor Chemicals Private Limited
Material, balance of Telmisartan Stage-3
Batch Size:100kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-2 67.00 Stage-3 110.00 1,7'-Dimethyl-2'-propyl-3' a,4',5',6',7',7'a-hexahydro-1H, 3'H-[2,5']bibenzoimidazolyl
68.15 Acetone recovery 475.00
Potassium Hydroxide 12.25 Acetone loss 15.00 Acetone 500.00 Effluent water 403.95 Water 400.00 (Water-400,
Generated water-3.95,) 0
By product (Potassium bromide-26.05)
26.05
Organic Residue 17.40 Process Residue-7.40
Distillation Residue-10 (Acetone-10)
Total 1047.40 Total 1047.40
Material, balance of Telmisartan Stage-4
Batch Size:100kg Name of the input Quantity
in Kg Name of the output Quantity
in Kg Stage-3 110.00 Telmisartan 100.00 Potassium Hydroxide 11.45 Methanol Recovery+
Generated Methanol 386.49
Acetic acid 12.32 Methanol Loss 12.00 DMF 100.00 MDC Recovery 380.00 Methanol 400.00 MDC Loss 8.00 MDC 400.00 DMF Recovery 95.00 Activated Carbon 5.00 DMF Loss 2.00 Water 600.00 Effluent water 620.13 (Water-600, Potassium
Acetate-20.13)
Spent Carbon 5.00 Organic Residue 30.15 Process Residue-7.15
Distillation Residue-23 (MDC-12,Methanol-8,DMF-3)
Total 1638.77 Total 1638.77
Manufacturing Process Page 233
ToR Amendment Tagoor Chemicals Private Limited
TERBINAFINE HYDROCHLORIDE
Process Description:
Stage-1
Napthyl methyl chloride reacts with Methyl amine in the presence of to give stage-1 product.
Stage-2
Pinacolone undergoes Alkylation in the presence of Potassium carbonate, Acetone and Hydrochloric acid to give stage-2 product.
Stage-3
Stage-2 Product reacts with acrolein in the presence of DIPE to give stage-3 product.
Stage-4
Step-A:
Stage-3 Product reacts with Isopropyl alcohol in presence of Aluminium Isopropoxide to give Step-A Product.
Step-B:
Step-A product reacts with Hydrochloric acid in presence of Toluene and Methanol to give stage-4 Product.
Stage-5
Stage-4 Product reacts with Stage-1 in presence of Potassium Carbonate, Methanol, Toluene and Ethyl acetate to give Terbinafine Hydochloride
Manufacturing Process Page 234
ToR Amendment Tagoor Chemicals Private Limited
TERBINAFINE HYDROCHLORIDE
Route of synthesis:
Stage-1:
Methyl amine
H2N CH3
31.06
HCl
Napthyl methyl chloride
Cl
+
C11H9Cl
176.64 C12H14ClN
207.70
Methanol .
N-Methyl-1-napthalene methylamine HCl
NH3C CH3
Stage-2:
Pinacolone
CH3
OH3C
H3CH3C
C6H12O
100.15
H3C
H3C
H3C
CH
C6H10
82.14
3,3-Dimethyl-but-1-yne
+ K2CO3 +
138.20
Acetone+ 2 HCl
72.92
2 KCl
149.10
+ + CO22 H2O
36.04 44.01
Stage-3:
H3C
H3CH3C
CH
C6H10
82.14
3,3-Dimethyl-but-1-yne
+
Acrolein
OH2C
C3H4O
56.06
H3CH3C
H3C
CHO
6,6-Dimethyl-hept-2-en-4-ynal
+
C9H12O136.19
DIPE
H2
2.00
Manufacturing Process Page 235
ToR Amendment Tagoor Chemicals Private Limited
Stage-4:
Step-A
H3CH3C
H3C
CHO
6,6-Dimethyl-hept-2-en-4-ynal
C9H12O
136.19
+
Isopropyl alcohol
CH3H3C
OH
C3H8O
60.09
H3CH3C
H3C
OH
6,6-Dimethyl-hept-2-en-4-yn-1-ol
C9H14O138.20
Aluminium isopropoxide
+
Acetone
H3C
O
CH3
C3H6O
58.07
Step-B
H3CH3C
H3COH
6,6-Dimethyl-hept-2-en-4-yn-1-ol
C9H14O
138.20
+
36.5
HCl
H3C
H3C
H3C
Cl
1-Chloro-6,6-dimethyl-hept-2-en-4-yne
C9H13Cl
156.65
H2O+
18.0
Manufacturing Process Page 236
ToR Amendment Tagoor Chemicals Private Limited
Stage-5:
Toluene
1-Chloro-6,6-Dimethyl Hept-2-ene-4-yne
H3C
H3C CH3
Cl
C9H13Cl156.65
+
N
CH3H3CCH3
CH3
Terbinafine HydrochlorideC21H26ClN
327.89
+ KCl
+ 1/2K2CO3
69.10
74.55
+ 1/2CO2
22.0
+ 1/2H2O
9.0
. HCl
HCl
C12H14ClN
207.70
.
N-Methyl-1-napthalene methylamine HCl
NH3C CH3
Manufacturing Process Page 237
ToR Amendment Tagoor Chemicals Private Limited
Flow Chart
Stage-1
Stage-2
Stage-3
Stage-4
Stage-5
TERBINAFINE HYDOCHLORIDE
Napthyl methyl chlorideMono methyl amineTolueneMDC
Toluene RecoveryMDC RecoveryEffluent water
Pinacolone Potassium carboanteHydrochloric acidAcetone
Acetone RecoveryEffluent water
Stage-2Acrolein DIPE
DIPE RecoveryEffluent water
Stage-3Isopropyl alcoholHydrochloric acidToluene Methanol Aluminium Isopropoxide
Isopropyl alcohol RecoveryToluene RecoveryEffluent water
Stage-1Stage-4ToluenePotassium carbonateMethanol Ethyl acetate
Toluene RecoveryMetahnol RecoveryEffluent water
Manufacturing Process Page 238
ToR Amendment Tagoor Chemicals Private Limited
Material Balance:
Material Balance of Terbinafine Hydrochloride Stage-1
Batch Size: 250.0Kgs Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Napthyl methyl chloride 150.00 Stage-1 166.00 Mono methyl amine 27.00 Toluene Recovery 285.00 Toluene 300.00 Toluene Loss 10.00 MDC 500.00 MDC Recovery 475.00 Water 450.00 MDC Loss 15.00 Effluent water 453.00 (Water-450, Toluene-3) 0 Organic Residue 23.00 Process residue-11
Distillation residue-12 (Toluene-2, MDC-10)
Total 1427.00 Total 1427.00
Material Balance of Terbinafine Hydrochloride Stage-2
Batch Size: 250.0Kgs Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Pinacolone 100.00 Stage-3 77.00 Potassium carboante 138.00 Acetone Recovery 190.00 Hydrochloric acid 73.00 Acetone Loss 5.00 Acetone 200.00 Effluent water 584.85 Water 400.00 (Water-400,Generated water-35.98,
Potassium chloride-148.87)
Process emission 43.94 (Carbondioxide-43.94) Organic Residue 10.21 Process residue-5.21
Distillation residue-5 (Acetone-5)
Total 911.00 Total 911.00
Manufacturing Process Page 239
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Terbinafine Hydrochloride Stage-3
Batch Size: 250.0Kgs Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 77.00 Stage-2 122.00 Acrolein 52.55 DIPE Recovery 475.00 DIPE 500.00 DIPE Loss 25.00 Water 400.00 Effluent water 400.00 (Water-400) Process emission 1.88 (Hydrogen -1.88) Organic Residue 5.67 Process residue-5.67 Total 1029.55 Total 1029.55
Material Balance of Terbinafine Hydrochloride Stage-4
Batch Size: 250.00Kgs Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 122.00 Stge-4 126.00 Isopropyl alcohol 250.00 Isopropyl alcohol Recovery 190.00 Hydrochloric acid 31.00 Isopropyl alcohol Loss 5.00 Toluene 800.00 (Mixed Solvent)
Toluene recovery + Generated Acetone
832.00
Methanol 400.00 Toluene Loss 12.00 Aluminium Isopropoxide 20.00 Methanol Recovery 380.00 Water 500.00 Methanol Loss 10.00 Effluent water 538.23 (Water-500, Generated water-
15.23,Toluene-3,Aluminium isopropoxide-20)
0
Organic Residue 29.77 Process residue-13.77
Distillation residue-16 (Toluene-5, Methanol-10,Isopropylalcohol-1)
Total 2123 Total 2123
Manufacturing Process Page 240
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Terbinafine Hydrochloride Stage-5
Batch Size: 250.00Kgs Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 166.00 Terbinafine Hydrochloride 250.00 Stage-4 126.00 Toluene Recovery 475.00 Toluene 500.00 Toluene Loss 15.00 Potassium carbonate 56.00 Methanol recovery 380.00 Methanol 400.00 Methanol Loss 10.00 Ethyl acetate 500.00 Ethyl acetate Recovery 475.00 Water 450.00 Ethyl acetate Loss 15.00 Inorganic solid waste 59.58 (Potassium chloride-59.58) Effluent water 467.19 (Water-450, Generated water-7.19,
Toluene-5, Ethyl acetae-5)
Process Emission 17.58 (Carbon dioxide-17.58) Organic Residue 33.65 Process residue-13.65
Distillation residue-20 (Toluene-5, Ethyl acetate -5, Methanol-10)
Total 2198.00 Total 2198.00
VALSARTAN Process Description:
Stage-1
Step-A:
L-Valine reacts with Thionyl chloride in presence of Toluene to give Step-A product.
Step-B:
Step-A Product reacts with Methanol in presence of water to give Stage-1 Product.
Stage-2:
Stage-1 product reacts with 4-Bromomethyl-biphenyl-2-carbonitrile in presence of Toluene to give Stage-2 product.
Stage-3
Stage-2 product reacts with Valeryl chloride in presence of Toluene to give Stage-3 product.
Manufacturing Process Page 241
ToR Amendment Tagoor Chemicals Private Limited
Stage-4
Stage-3 product reacts with Sodium azide, Tri butyl tin chloride undergoes Hydrogenation in presence of Toluene, MDC and n-Hexane t give Valsartan.
Route of Synthesis:
Stage-1
Step-A
L-Valine
C5H11NO2
117.15
NH2
CH3
H3C OH
O
+ SOCl2
NH2
CH3
H3C Cl
O+ SO2
HCl
Thionyl Chloride
118.972-Amino-3-methyl-butyryl chloride
hydrochlorideC5H11Cl2NO
172.05
64.06
Toluene
Step-B
NH2
CH3
H3C Cl
O
+H
Cl
2-Amino-3-methyl-butyryl chloride
hydrochlorideC5H11Cl2NO
172.05
CH3OH
NH2
CH3
H3C OCH3
O HCl + HCl
32.04 2-Amino-3-methyl-butyric Acid methyl ester hydrochloride
36.46
C6H14NO2Cl
167.63
Methanol
Manufacturing Process Page 242
ToR Amendment Tagoor Chemicals Private Limited
Stage-2
NH2
CH3
H3C OCH3
O HCl
2-Amino-3-methyl-butyric Acid methyl ester hydrochloride
C6H14NO2Cl
167.63
4-Bromomethyl-biphenyl-2-carbonitrile
N
Br
+
N
O
O
NH
2-[(2-Cyano-biphenyl-4-ylmethyl)-amino]-3-methyl-butyric acid methyl ester
C14H10BrN
272.14
+
Potassium Carbonate
138.21
Toluene
C20H22N2O2
322.40
+ KBr +
K2CO3
KCl + CO2 + H2O
119.0 74.55 44.0 18.0
Manufacturing Process Page 243
ToR Amendment Tagoor Chemicals Private Limited
Stage-3
N
O
O
NH
2-[(2-Cyano-biphenyl-4-ylmethyl)-amino]-3-methyl-butyric acid methyl ester
C20H22N2O2
322.40
Valeryl Chloride
O
Cl+ + NaHCO3
Sodium bicarbonate
Toluene
C5H9ClO
120.58
84.0
OO
N
N
O
2-[(2-Cyano-biphenyl-4-ylmethyl)-pentanoyl-amino]-3-methyl-butyric acid methyl ester
C25H30N2O3
406.52
+ NaCl + CO2 + H2O
58.44 44.0 18.0
Manufacturing Process Page 244
ToR Amendment Tagoor Chemicals Private Limited
Stage-4
O
O
N
N
O
2-[(2-Cyano-biphenyl-4-ylmethyl)-pentanoyl-amino]-3-methyl-butyric acid methyl ester
C25H30N2O3
406.52
O
OH
N
O
NN
HN
N
+ NaN3 +
Tributyl tin chloride
SnCl
+ H2
Hydrogen Sodium Azide
2.0 65.0 C12H27ClSn
325.5
Valsartan
C24H29N5O3
435.5
+ SnH3C
+ NaCl
Tributyl methyl stannane
C13H30Sn
305.0
58.46
TolueneMDC
Manufacturing Process Page 245
ToR Amendment Tagoor Chemicals Private Limited
Flow-Chart
Stage-1
Stage-2
L-ValineThionyl ChlorideMethanolToluene
Methanol RecoveryToluene Recovery
Stage-14-Bromomethyl-biphenyl-2-carbonitrilePotassium carbonateToluene
Toluene RecoveryEffluent water
Stage-2Valeryl ChlorideTolueneTEASodium bicarbonateSodium Sulphate
Stage-3Toluene RecoveryEffluent water
Stage-3Sodium AzideTri butyl tin chlorideHydrogen Sodium hydroxideXyleneTolueneMDCN-HexaneActivated Carbon
Stage-4
Xylene RecoveryMDC RecoveryToluene RecoveryEffluent watetr
VALSARTAN
Manufacturing Process Page 246
ToR Amendment Tagoor Chemicals Private Limited
VALSARTAN Material Balance:
Material Balance of Valsartan Stage-1
Batch Size: 100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg L-Valine 45.00 Stgae-1 51.00 Thionyl Chloride 45.67 Methanol Recovery 380.00 Methanol 409.00 Methanol Loss 12.00 Toluene 400.00 Toluene Recovery 380.00 Toluene Loss 12.00 Process Emission 34.06 (Sulfur dioxide-24.57, Hydrogen
Chloride-9.49) 0
Organic Residue 30.61 Process residue -14.61,
Distillation residue -16 (Methanol-8, Toluene-8)
Total 899.67 Total 899.67
Material Balance of Valsartan Stage-2
Batch Size: 100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-1 51.00 Stage-2 87.00 4-Bromomethyl-biphenyl-2-carbonitrile
82.77 Toluene Recovery 570.0
Potassium carbonate 42.02 Toluene Loss 20.00 Toluene 600.00 Effluent Water 569.04 Water 500.00 (Water-500,Generated water-5.45,
Potassium chloride-22.44, Potassium Bromide-36.15, Toluene-5)
0
Process Emission 13.36 (Carbon dioxide-13.36) 0 Organic Residue 16.39 Process residue -11.39
Distillation residue -5 (Toluene-5)
Total 1275.79 Total 1275.79
Manufacturing Process Page 247
ToR Amendment Tagoor Chemicals Private Limited
Material Balance of Valsartan Stage-3
Batch Size: 100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-2 87.00 Stage-3 104.00 Valeryl Chloride 32.53 Toluene Recovery 665.00 Toluene 700.00 Toluene Loss 20.00 TEA 20.00 Effluent Water 448.52 Sodium bicarbonate 22.62 (Water-400,Generated water-
4.78, Sodium chloride-15.74, TEA-20,Toluene-8)
Sodium Sulphate 10.00 Inorganic Solid Waste 10.00 Water 400.00 (Sodium Sulphate) Process Emission 11.83 (Carbon dioxide-11.83) Organic Residue 12.80 Process residue -5.8,
Distillation residue -7 (Toluene-7)
Total 1272.15 Total 1272.15
Material Balance of Valsartan Stage-4
Batch Size: 100Kg Name of the input Quantity
in Kg Name of the out put Quantity
in Kg Stage-3 104.00 Valsartan Pharma 100.00 Sodium Azide 16.55 Toluene Recovery 665.00 Tri butyl tin chloride 83.20 Toluene Loss 20.00 Hydrogen 0.42 MDC Recovery 475.00 Sodium hydroxide 20.00 MDC Loss 15.00 Xylene 240.00 Xylene Recovery 228.00 Toluene 700.00 Xylene Loss 12.00 MDC 500.00 N-Hexane Recovery 190.00 N-Hexane 200.00 N-Hexane Loss 10.00 Activated Carbon 10.00 Effluent Water 832.87 Water 800.00 (Water-800, Sodium Chloride-
14.87,Toluene-8, Acetic Acid-10) 0
Spent Carbon 10.00 Organic Residue 116.30 Process residue –99.3
Organic Impurities-21.3, (Tri butyl-methyl –stannane-78) Distillation residue- 17 (Toluene-7, MDC-10)
Total 2674.17 Total 2674.17
Manufacturing Process Page 248
PRE - FEASIBILITY REPORT
TOR AMENDMENT
For
Expansion of Existing Bulk Drug & Intermediates
Manufacturing Unit
at
Survey No: 32, Tupakulagudem (Village), Tallapudi
(Mandal), West Godavari (Dist.), Andhra Pradesh
By
TAGOOR CHEMICALS PRIVATE LIMITED (Formerly known as Vensar Laboratories Pvt Ltd)
Office address:
Duplex No: 29, Lakshmi Gayatri Enclave, Aditya Nagar, KPHB,
Kukatpally, Hyderabad
MAY - 2018
Contents
S. No. Description Page no.
1.0 Executive Summary 1
2.0 Introduction of the Proposed Project 2
2.1 Project Proponent 2
2.2 Brief description of the project 3
2.3 Need for the project and its importance to the country and or
region 3-4
2.4 Demand-Supply Gap. 4-5
2.5 Employment Generation(Direct and Indirect) due to the project
5
3.0 Project description 5
3.1 Product and Production Capacity 8
3.2 Raw materials required and Quantities 11
3.3 Manufacturing Process 11
3.4 Resource – Utilize and Recycling 12
3.4.1 Water 12
3.4.2 Power Requirement 12
3.4.3 Fuel Requirement 12
3.5 Quantity of wastes generated 12
3.5.1 Waste Water Generation and utilization 12 - 13
3.5.2 Solid waste generation and Disposal 13
3.6 Schematic representations of the feasibility drawing which give information of EIA purpose
14
4.0 Site Analysis 15
4.1 Connectivity 15
4.2 Land Form, Land use and Land ownership. 15
4.3 Existing Infrastructure 15
4.4 Soil classification 15
4.5 Climatic data from secondary sources 15
4.6 Social Infrastructure available 16
5.0 Planning in brief 16
6.0 Proposed infrastructure 16
6.1 Industrial Area 16
6.2 Residential Area 16
6.3 Green Belt 16
6.4 Social Infrastructure 16 - 17
6.5 Water management 17
6.6 Sewerage System 17
6.7 Industrial Waste Management 17
7.0 Rehabilitation and Resettlement (R&R) Plan 17
8.0 Project Schedule and Cost estimate 17
9.0 Analysis of project 17
LIST OF TABLES
Table No Description Page no.
3.1 Proposed Products and Existing Products and their Production Capacities
8 - 10
3.2 List of By-Products 10 - 11
3.3 Water Requirement Details 13
3.4 Wastewater generation and Treatment Method 13
3.5 Solid and hazardous waste generation and Disposal 13 -14
LIST OF FIGURES
Figure No Description Page no.
3.1 Location Map 6
3.2 Google Earth Map Showing Tagoor Chemicals Private
Limited
7
LIST OF FLOW CHART
Flow Chart No
Description Page no.
3.1 Generalized Flow Chart for Bulk Drug Manufacturing 11
Tagoor Chemicals Private Limited Pre Feasibility Report
Page 1
1.0 EXECUTIVE SUMMARY
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt
Ltd) is a partnership firm and it is registered office at Duplex No: 29, Lakshmi Gayatri
Enclave, Aditya Nagar, KPHB, Kukatpally, Hyderabad Telangana State.
S. No Parameter Description
1 Project Location Survey No: 32, Tupakulagudem (V) Tallapudi
(M), West Godavari (Dist.), Andhra Pradesh
2 Category of Project as per EIA Notification & Amendments
5(f) “A”
3 Project cost As per Granted ToR: 39 Cores
Amendment Required : 45 Cores
4 Plot area 10.35 Acres (41885 Sq.m)
5 Proposed Products Proposed Products List is mentioned in section
3.1
Resources
6 (I)Electricity
Requirement
As per Granted ToR: 800 KVA
Amendment Required : 2000 KVA
7 Source of electricity Andhra Pradesh Southern Power Distribution
Company Limited (APSPDCL)
D. G. Sets As per Granted ToR: 250 KVA & 500KVA
Amendment Required : 1000KVA X 2 no’s
(II)Water consumption
As per Granted ToR: 190 KLD
Amendment Required : 396 KLD
(Water Recovered from Process is 81.5 KLD & Water Recycled from ZLD System is 114.5 KLD)
8 Source of water
As per Granted ToR: Ground Water
Amendment Required : Surface water
Allotment from State Government /Ground
Water
Waste water generation As per Granted ToR: 80 KLD
Amendment Required : 144 KLD
(III)Boiler
As per Granted ToR:
Existing: 6.0 TPH Coal fired/ Agro waste fired
Boiler & 2,00,000 kcal/hr. Thermo pack Boiler
(Continued);
Tagoor Chemicals Private Limited Pre Feasibility Report
Page 2
Proposed: 4.0 TPH Coal fired/ Agro waste fired Boiler Amendment Required :
Existing: 6.0 TPH Coal fired/ Agro waste fired
Boiler will be kept as Standby
The existing 2,00,000 kcal/hr. Thermo pack
Boiler will be Continued
Proposed: 12.0 TPH Coal fired/ Agro waste fired Boiler
9 (IV)Fuel
Coal Requirement As per Granted ToR: 33.00 TPD
Amendment Required : 48.75 TPD
10 Mode of disposal Zero Liquid Discharge System
11 Solid waste generation Mentioned in Para 3.5.2 of report
12 Nearest Highway National Highway NH - 16: 26 KMs (SE) (Rajahmundry – Anakapalle)
13 Nearest Railway Station Kovvuru Railway station – 22.0 KMs (SE)
14 Nearest Airport Rajahmundry Airport – 24.00 KMs (ESE)
2.0 INTRODUCTION OF THE PROJECT
The objective of this pre- feasibility study is to provide information on proposed to
Expansion of Existing Bulk Drug & Intermediate manufacturing unit of Tagoor
Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd)
located at Sy No. 32, Tupakulagudem Village, Tallapudi Mandal, West Godavari
District, Andhra Pradesh.
2.1 Project Proponent
Mr. Penmetsa Subramanyam Raju, Managing partner of the company is young
and energetic personality with vast experience in pharmaceutical industry
Mr. Subramanya Raju has work experience of more than 18 years in bulk drugs
industry. He has worked in senior position as Director-manufacturing in Vasudha
group of industries and helped to emerge as one of the leading group in bulk drug
industry. During his tenure in Vasudha Pharma Chem Limited, he had managed 3
units situated in jeedimetla, kazipally, and Visakhapatnam looking after production,
research and development, packing, dispatch of the finished intermediates and APIs
Tagoor Chemicals Private Limited Pre Feasibility Report
Page 3
at right time, conforming to the specifications. Added to this, he is actively involved in
discussing with the customers for extracting business by increasing the yields and
reducing production cost to meet the demand of the customers. He has visited many
countries in Europe & Asia for exhibiting the bulk drug products. Mr. Subramanyam
Raju is also Managing Partner of Sri Venkateswara Industries which manufactures
the intermediates & bulk drugs, situated in Hyderabad. Considering his skills and
abilities, M/s Shree Jaya Laboratories Pvt Ltd., have offered him the post of Director
during February 2012 and he assumed charge of the Director during February 2012
and has taken charge as Chairman during April 2013 looking after the entire
production, research and development activities of the organization. He has
improved the turnover of the company from 28 crores to 120 crores within a short
span of one year.
Mr. Subramanyam Raju is experienced in manufacturing, process development,
project management, scale up to operations, quality systems and the aqua culturing
technically.
Mr. Subramanyam Raju was also awarded Hon. Doctorate by the international
university in Colombo during November 2013. He has also acquired more than
20acres of land in west Godavari district of Tallapudi Mandal for establishment of
Vensar and Vensub laboratories for manufacturing APIs. All the relevant licenses for
commencement of the units were obtained and the land is made ready for
construction works.
Dr. Pericherla Kasiviswanadharaju, the partner of the company is technically
qualified person, having rich experience in organic synthesis. He recently finished his
Ph.D from prestigious institute BITS Pilani, Rajasthan and his technical background
is an additional asset to the industry. Presently, he is involved in purchase,
marketing and research and development departments.
2.2 Brief description of the project.
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt
Ltd) is proposed to expansion of Existing Bulk Drug & Intermediate manufacturing
unit at Survey No: 32, Tupakulagudem (V) Tallapudi (M), West Godavari (Dist.),
Andhra Pradesh.
Tagoor Chemicals Private Limited Pre Feasibility Report
Page 4
2.3 Need for the project and its importance to the country and region
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt
Ltd) is proposed to expansion of existing Bulk Drug & Intermediate manufacturing
unit at Survey No: 32, Tupakulagudem (V) Tallapudi (M), West Godavari (Dist.),
Andhra Pradesh.
Availability of the well-connected road and railway network for easy transportation
of the construction equipments and materials, Raw materials and finished
products.
Easy availability of skilled and unskilled labor for construction of Plant and its
operation.
The Indian pharmaceutical industry currently tops the chart amongst India's science-
based industries with wide ranging capabilities in the complex field of drug
manufacture and technology. A highly organized sector, the Indian pharmaceutical
industry is estimated to be worth $ 4.5 billion, growing at about 8 to 9 percent
annually. It ranks very high amongst all the third world countries, in terms of
technology, quality and the vast range of medicines that are manufactured. It ranges
from simple headache pills to sophisticated antibiotics and complex cardiac
compounds; almost every type of medicine is now made in the Indian
pharmaceutical industry.
The Indian pharmaceutical sector is highly fragmented with more than 20,000
registered units. It has expanded drastically in the last two decades. The
Pharmaceutical and Chemical industry in India is an extremely fragmented market
with severe price competition and government price control The Pharmaceutical
industry in India meets around 70% of the country's demand for bulk drugs, drug
intermediates, pharmaceutical formulations, chemicals, tablets, capsules, orals, and
injectibles. There are approximately 250 large units and about 8000 Small Scale
Units, which form the core of the pharmaceutical industry in India (including 5 Central
Public Sector Units).
The Indian pharma industry, which is expected to grow over 16 per cent per annum
between 2017 and 2020, will outperform the global pharma industry, which is set to
grow at an annual rate of 5 per cent between the same period!. The market is
expected to grow to US$ 55 billion by 2020, thereby emerging as the sixth largest
pharmaceutical market globally by absolute size, as stated Indian Ambassador to the
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US. Branded generics dominate the pharmaceuticals market, constituting nearly 80
per cent of the market share (in terms of revenues).
India has also maintained its lead over China in pharmaceutical exports with a year-
on-year growth of 11.44 per cent to US$ 12.91 billion in FY 2015-16, according to
data from the Ministry of Commerce and Industry. Imports of pharmaceutical
products rose marginally by 0.80 per cent year-on-year to US$ 1,641.15 million.
Overall drug approvals given by the US Food and Drug Administration (USFDA) to
Indian companies have nearly doubled to 201 in FY 2015-16 from 109 in FY 2014-
15. The country accounts for around 30 per cent (by volume) and about 10 per cent
(value) in the US$ 70-80 billion US generics market.
2.4 Demand-Supply Gap.
There is a quite considerable gap between supply and demand for, fine chemicals,
bulk drugs and intermediates. Very few players are in the market who can offer
continuous supply. The company wants to bridge this gap between demand and
supply by expanding the production capacity and thereby, making good business.
Company's marketing edge comes from its direct and close contact with the
customers. Their products are major strength of their customers. Each stage of their
product is been monitored /checked for their quality to ensure quality product
reaches their customer. They plan to launch new products every year to satisfy the
need of their customers as per the market demand.
2.5 Employment Generation (Direct and Indirect) due to the project
Approximate employment generation due to proposed unit is 130. Apart from this
there will be significant non estimated employment generation at the supplier firms
and service industry providing services to the company. Company shall be giving
preference to people from economically weaker sections for employment in various
semi-skilled/unskilled jobs thereby contributing to their upliftment.
3.0 Project Description
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt
Ltd) is proposing the Expansion of existing Bulk Drug and Intermediates
Manufacturing Unit with production capacity of 200.00 TPM
The Location map is shown at Figure - 3.1 and Google earth map showing Tagoor
Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt Ltd) plant is
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shown at Figure - 3.2.
The site central GPS - coordinates are
Latitude: 17009’27.26” North
Longitude: 81035’32.23” East
The project site does not offer any negative impact on the local area, but rather it has
a positive impact on socio economic conditions of the habitants around it because of
employment to locals.
The Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt
Ltd) is 26 kms away from National Highway NH – 16 and 22 kms from
Kovvur Railway station.
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FIGURE 3.1: LOCATION MAP
Project Site
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FIGURE 3.2: GOOGLE EARTH MAP SHOWING TAGOOR CHEMICALS PRIVATE LIMITED
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3.1 Proposed Products and Existing Products and their Production Capacities
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt
Ltd) is proposing to Expansion of existing Bulk Drug and Intermediates
Manufacturing Unit Capacity of 200.00 TPM and the list of proposed products and
Existing Products are shown in Table 3.1 & 3.2.
Table 3.1: Proposed Products and Quantities
S. No.
Product Name
Production Capacity
Ton/ Month
CAS No. Therapeutic
category
1 Amitriptyline 10.00 549-18-8 Antidepressant
2 Atrovastatin Calcium 5.00 134523-03-8 Hypercholesterolemia
3 Bupropion 5.00 34841-39-9 Anti depressant
4 Clopidogrelbisulfate 5.00 135046-48-9 Antithrombotic
5 Cyclobenzaprine HCl 5.00 6202-23-9 Muscle relaxant
6 Cyproheptadine HCl 10.00 41354-29-4 Anti allergic
7 Desloratadine 5.00 100649-74-8 Antihistamine
8 Domperidone 30.00 99497-03-7 Anti emetic
9 Domperidone maleate 2.00 99497-03-7 Anti emetic
10 Donepezil HCl 1.00 12004-70-3 Alzheimer’s disease
11 Ebastine 5.00 90729-43-4 Anti allergic
12 Esomeprazole Sodium 3.00 161796-78-7 Anti ulcerative
13 Esomeprazole Magnesium trihydrate
3.00 217087-09-7 Anti ulcerative
14 Fexofenadine Hydrochloride
5.00 143439-40-8 Anti histamine
15 Haloperidol 2.00 52-86-8 Antipsychotic
16 Itopride Hydrochloride 2.00 122892-31-3 Antispasmodics
17 Itraconazole 15.00 84625-61-6 Antifungal
18 Ketrolac Tromethane 2.00 74103-07-4 Anti Inflammatory
19 Lansoprazole 10.00 103577-45-3 Ant ulcerative
20 Loperamide Hydrochloride 10.00 34552-83-5 Anti diarrhea agent
21 Losartan Potassium 20.00 124750-99-8 Anti Hypertensive
22 Nebivolol HCl 2.00 99200-09-6 Anti Hypertensive
23 Nortriptyline HCl 2.00 894-71-3 Anti depressant
24 Omeprazole 60.00 95510-70-6 Ant ulcerative
25 Omeprazole Sodium 2.00 95510-70-6 Ant ulcerative
26 Omeprazole Magnesium Dihydrate
2.00 95382-33-5 Ant ulcerative
27 Oxatomide 1.00 60607-34-3 Antihistamine
28
Pantoprazole Sodium Sesqui Hydrate
20.00 164579-32-2 Ant ulcerative
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S. No.
Product Name
Production Capacity
Ton/ Month
CAS No. Therapeutic
category
29 Pimozide 2.00 2062-78-4 Antipsychotic
30 Pregabalin 2.00 148553-50-8 Epileptic
31 Quetiapine Hemifumarate 2.00 111974-72-2 Antipsychotic
32 Rabeprazole Sodium 20.00 117976-90-6 Ant ulcerative
33 Rupatadine fumarate 2.00 182349-12-8 Antihistamine
34 Telmisartan 2.00 144701-48-4 Anti Hypertensive
35 Terbinafine hydrochloride 15.00 78628-80-5 Anti fungal
36 Valsartan 2.00 137862-59-4 Anti Hypertensive
37 1-Benzy-4-piperidone 5.00 3612-20-2 Drug Intermediate
38 1-Benzyl-4-chloropiperidine
5.00 67848-71-9 Drug Intermediate
39 1-Benzylpiperidin-4-ol 5.00 4727-72-4 Drug Intermediate
40 1-Methylpiperidin-4-amine 5.00 41838-46-4 Drug Intermediate
41 4-Aminopiperidine 5.00 13035-19-3 Drug Intermediate
42 4-Hydroxy piperidine 5.00 5382-16-1 Drug Intermediate
43 4-Phenylpiperidine 1.00 771-99-3 Drug Intermediate
44 4-piperidinopiperidine 1.00 4897-50-1 Drug Intermediate
45 N-tert-Butoxycarbonyl-4-hydroxy piperidine
5.00 109384-19-2 Drug Intermediate
Total ( Worst Combination of any 10 Products at any given point of time)
200.00
Note:
The above Listed Products, we will manufacture either Finished Product or any
Intermediate stage of finished Product as per given quantity by not increasing the
production capacity of 200 MT/Month.
Table 3.2: By Products
S. No.
Product Name By product Quantity in
Kg /Day
1
Clopidogrel Bisulphate
Ammonium sulphate 5260 Omeprazole
Domperidone
2
Domperidone
Sodium bromide 948 Cyclobenzaprinehydrochloride
Itraconazole
3 Cyclobenzaprinehydrochloride Magnesium Chloride 239
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S. No.
Product Name By product Quantity in
Kg /Day
Cyproheptadine Hydrochloride
Desloratadine
4 Desloratadine
Potassium chloride 226 Ebastine
5 Ebastine Aluminium chloride solution (12%)
667
6 Itraconazole
Potassium bromide 117 Telmisartan
7
Pantoprazole sodium sesquihydrate Ammonium chloride 2215.57 Domperidone
8 Pantoprazole sodium sesquihydrate
Ammonium acetate 234
Acetic acid 506
Ammonium phosphate 773.50
Sodium methyl sulphate 632
9
Pantoprazole sodium sesquihydrate
Sodium acetate 1615.60 Domperidone
Rabeprazole sodium
Omeprazole
10 Omeprazole Sodium nitrite 817.50
11 Domperidone Methanol 299
12 Losartan Potassium Trityl alcohol 43.50
Total 14593.67
Note: The By-Products will be produced according to the combination of required
products manufacturing.
3.2 Raw materials required and Quantities
All the raw materials required for manufacturing of above products will be sourced
from local market.
3.3 Manufacturing Process
The manufacturing process of bulk drugs and Intermediates consists of chemical
synthesis extending to stages of processing involving different type of chemical
reactions. The generalized Flow chart for bulk drug manufacturing is shown in Flow
chart 3.1.
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Flow Chart 3.1: Generalized Flow Chart for Bulk Drug Manufacturing
3.4 Resource – Utilize & Recycling
3.4.1 Water
Water requirement of the project for domestic and industrial activity during operation
phase will be 396.00 KLD. The water requirement will be met through ground water
sources. The detailed water requirement shown in below Table 3.3
Table 3.3: WATER REQUIREMENT DETAILS
S.No Purpose Water consumption
In KLD
1 Process 171.0
2 Washings 6.0
3 Boiler make up 71.0
4 Cooling towers make up 119.0
5 Scrubbing system 18.0
6 Domestic 6.0
7 Gardening 5.0 Total 396.0
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Total Water consumption of 396 KLD, 196 KLD of water will be recovered (from
Process 81.5 KLD & Water Recycled from ZLD System 114.5 KLD). Hence, Total
fresh water requirement is 396KLD-196 KLD=200 KLD.
3.4.2 Power Requirement
Power requirement of proposed project will be made available through Andhra
Pradesh Southern Power Distribution Company Limited (APSPDCL). The total
power requirement for the unit is 2000 KVA respectively
D.G. sets of Existing 250 KVA will be dropped and Proposed to install 1000 KVA DG
Set 2 no’s to meet the emergency power requirement of the plant.
3.4.3 Fuel Requirement
The existing 6.0 TPH Coal fired/ Agro waste fired Boiler will be kept as standby and
2,00,000 kcal/hr Thermo pack Boiler will be Continued.
Proposed to install 12.0 TPH Coal fired/ Agro waste fired Boiler and total fuel
requirement of coal will be around 48.75 MT /Day and it will be procured from local
sources.
3.5 Quantity of wastes to be generated
3.5.1 Waste Water Generation and utilization
Total effluent will generate in the project is 144.00 KLD. The treated water will be
reused for plant operations.
The HTDS waste water from Process after neutralization taken for treatment in
stripper followed by MEE and ATFD, vapor condensate collected and transferred to
Biological Treatment. LTDS waste water including domestic sewage, floor Washes,
Utilities waste water taken along with Vapour Condensate from MEE & ATFD for
Biological Treatment. Treated effluent from BTP sent to RO, RO permeate collected
and RO rejects are sent to MEE followed by ATFD for evaporation and separation of
salts. Evaporation salts collected and sent to TSDF. MEE & ATFD vapour
condensates collected & reused along with RO permeate in plant operations.
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Table 3.4: Waste water generation and Treatment Method
S. No
Unit HTDS KLD
LTDS KLD
Effluent Generation
in KLD Treatment Method
1 Process 58.0 34.0 92.0 HTDS effluent sent to ETP with MEE System LTDS effluents treated in ETP – RO Plant / RO Rejects to MEE System and RO permeate to reuse, Condensate from MEE to reuse and MEE residue to ATFD.
2 Washings 0.00 6.0 6.00
3 Boiler Blow down 0.00 10.0 10.0
4 Cooling towers Blow down
0.00 15.5 15.5
5 Scrubbing system 15.00 0.00 15.00
6 Domestic 0.00 5.5 5.5
Total 73 71 144
3.5.2 Solid and Hazardous waste generation and Disposal
The types of Solid and Hazardous wastes generated from the project, method of
disposal is shown in below table 3.5.
Table 3.5: Solid / Hazardous waste generation and Disposal
S. No
Name of the Hazardous Waste
Quantity
Disposal Method
1 Organic waste (Process Residue)
2133 Kg/Day
Sent to Cement Industries
2 Spent Carbon
281.50 Kg/Day
Sent to Cement Industries
3 Solvent Distillation Residue
1766 Kg/Day
Sent to Cement Industries
4 Inorganic Waste
796 Kg/Day
Sent to TSDF
5 Spent Mixed Solvents
4000 Kg/Day
Sent to authorized recyclers/Cement Industries
6 ETP Sludge
500 .00 Kg/Day
Sent to TSDF
7 MEE Salts
8736 Kg/Day
Sent to TSDF
8 Organic Evaporative Liquid ( from MEE Stripper)
1460 Kg/Day
Sent to Cement Industry
9 Used Oils 500L/Annum
SPCB Authorized Agencies for Reprocessing/Recycling
10
Detoxified Containers 800 No’s /
Month After Detoxification sent to outside agencies.
11 Used Lead Acid Batteries
4 No’s/ Annum
Send back to suppliers for buyback of New Batteries
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S. No
Name of the Hazardous Waste
Quantity
Disposal Method
12 Ash from boiler 17100 Kg/Day
Sent to Brick Manufacturers
3.6 Schematic representations of the feasibility drawing which give
information of EIA purpose.
The applicability of the S.O.1533 for the proposed project was explored by
considering different possibilities & provision made in the said notification.
Considering the products & project location of the proposed project it is noticed that
the proposed project falls under Category 5 (f) “A” of the Schedule-I of EIA
Notification S. O. 1533
As per the provision of the SO 1533, it is necessary to get Environmental Clearance
by applying to MoEF&CC along with the Environmental Impacts Assessment Study
Report for the proposed project prior to commissioning of the project activities.
Therefore the EIA is required to conduct to comply with provisions of SO 1533 made
for Category 5 (f) “A” of schedule –I of the notification.
4.0. Site Analysis
4.1 Connectivity
Tagoor Chemicals Private Limited (Formerly known as Vensar Laboratories Pvt
Ltd) located at Survey No: 32, Tupakulagudem (V) Tallapudi (M), West Godavari
(Dist.), Andhra Pradesh.
Gopavaram village is at a distance of 1.43 KMs in N Direction from the site.
Kovvur is a Town; it is at a distance of 20 KMs in SE side from the project site.
Site is at a distance of 24 KMs from Rajahmundry in SE direction.
Nearest State Highway from the site is SH-42 (Koyyalagudem- Nallajerla) at a
distance of 17 KMs in W side from the project site.
Nearest National Highway from the site is NH-5 (Rajahmundry - Anakapalle) at a
distance of 26 KMs in SE side from the project site.
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4.2 Land Form, Land use and Land ownership.
The land use of the Area of 10.35 Acres (41885 Sq.m) will be permanently changed
to industrial purpose.
4.3 Existing Infrastructure.
The Proposed project proposed to Expansion of existing Bulk Drug and
Intermediates Manufacturing Unit which is 26 kms away from NH-17 and Mandal
head quarter Tallapudi is 8.50 kms (ESE) from the project site.
4.4 Soil classification
The predominant soils in the district are Sandy loams, black cotton soils and coastal
sands.
4.5 Climatic data from secondary sources.
Annual Max Temp is 36.8.0C
Annual Min Temp is 19.50C
Normal Annual Rainfall is 1078 mm
4.6 Social Infrastructure available.
Well developed social infrastructure facilities are available at nearby Habitations.
5.0 Planning Brief
Proposed plant activities will be started after getting statutory clearance form related
authorities. The project will be completed within two years. Further project
management will take care of all the rules and regulation of statutory authority and
provide all necessary control measures
6.0 Proposed Infrastructure
6.1 Industrial Area
The infrastructure and other facilities are already well developed in Tallapudi, which
is a Mandal head quarter.
6.2 Residential Area
The employees who will work in the industry are from nearby villages and hence no
proposal for residential area for employees.
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6.3 Green Belt:
14867 SQM (35.50 %) of Green Belt will be developed and maintained.
6.4 Social Infrastructure:
Facilities like roads, communication, Banks, ATM's and medical facilities are
available.
Amenities:
Education Schools including middle, secondary and higher secondary schools, social
welfare hostels
Medical and Health Community Health Centre & Primary Health center are
available in Tallapudi which is 8.50 kms ESE of proposed project site.
Power and water- All the villages are electrified and drinking water facilities are
extended to all villages.
Rail and Road- The project site is very well connected by road through National
Highway No. 16 and nearest railway station is Kovvur.
6.5 Water management
Water requirement will be met through ground water.
6.6 Sewerage System
There will be no discharge of industrial effluent as company proposing Zero Liquid
Discharge (ZLD) system. The treated effluent will be reused.
6.7 Industrial Waste Management
Due to proposed project, the effluent from cooling and Plant/Equipment washing will
be generated and treated in the well designed Effluent Treatment Plant. The treated
effluent will be reused.
7.0 Rehabilitation and Resettlement (R & R) Plan
Rehabilitation & Resettlement (R & R) plan is not applicable to this proposed project.
8.0 Project Schedule & Cost Estimates
Proposed project activities will be started after getting statutory clearance form
related authorities. The project will be completed within two years.
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The project cost for proposed Project is 4500 Lakhs (45 Crores) will be used for
constructing additional building, Equipments & misc.
9.0 Analysis of Benefits to proposal
Local people will get direct financial benefit by way of employment.
Local people will get some contracts of supply and services to get indirect
income.
Company will contribute in improving education and health facilities in nearby
area.