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LIST OF ENCLOSURES

S. No Content Annexure

1 CFE Copy Enclosure -I

2 CFO Copy Enclosure -II

3 Land Documents Enclosure-III

COPY OF CFE

COPY OF CFO

LAND DOCUMENT

LIST OF ANNEXURES

S. No Content Annexure

1 List of Products Annexure-I

2 Manufaturing Process Description Annexure-II

3 Water Consumption Details Annexure-III

4 Hazardous waste

Annexure-IV 5 Industrial Process waste

6 Sewage sludge

7 Hazardous & Solid waste

8 Stack Emission Details Annexure-V 9 Process Emission Details Annexure-VI

10 List of Raw Materials Annexure- VII

11 List of By - Products Annexure-VIII

12 Waste water Details Annexure-IX

Additional info M/s. Shree Jaya Laboratories Pvt Ltd

Prepared By Rightsource Industrial Solutions Pvt. Ltd. Page 1

Annexure - I

LIST OF PROPOSED PRODUCTS

S. No Name of the Product CAS Number

Therapeutic Category

Quantity In Kg/Month

1 Benzyl Magnesium chloride 6921-34-2 Organic Reagent 10000.00 2 Butyl Magnesium Chloride 693-04-9 Organic Reagent 15000.00 3 Domperidone 57808-66-9 Antiemetic. 5000.00 4 Escitalopram oxalate 219861-08-2 Antidepressant. 3000.00

5 Esomeprazole Magnesium trihydrate 217087-10-0 Antiulcer Agent 5000.00

6 Ethyl magnesium Chloride 925-90-6 Organic Reagent 15000.00

7 Linezolid 165800-03-3 Antibiotic 2000.00 8 Loperamide hydrochloride 34552-83-5 Ant diarrheal 2000.00 9 Magnesium tert.Butoxide 32149-57-8. Organic Reagent 15000.00

10 Metformin hydrochloride 1115-70-4 Hypoglycemic 50000.00

11 Methyl magnesium chloride 676-58-4

Organic Reagent 20000.00

12 N,N-Dimethyl propyl magnesium chloride - Drug Intermediate 20000.00

13 Omeprazole 73590-58-6 Proton pump inhibitor. 20000.00

14 Pantoprazole sodium 138786-67-1 Gastric Acid Secretion Inhibitor

15000.00

15 Phenyl magnesium chloride 100-59-4

Organic Reagents 15000.00

16 Quetiapine Fumarate 111974-72-2 Antipsychotic, 5000.00

17 Rabeprazole Sodium 117976-90-6 Gastric Acid Secretion Inhibitor

5000.00

18 Sodium Methoxide 124-41-4 Antineoplastic 50000.00 19 Sodium tert butoxide 865-48-5 Organic Reagent 20000.00 20 Telmisartan 144701-48-4 Anti hypertensive 3000.00

Total 295000.00


Prepared By Rightsource Industrial Solutions Pvt. Ltd Page 2

Annexure - II

MANUFACTURING PROCESS

1. BENZYL MAGNESIUM CHLORIDE

Process Description:

Stage-1

Magnesium metal is charged into a clean and dry reactor under nitrogen purging.

Charge DEE & THF and start stirring. Raise the reactor temperature up to required

temperature. Start and continue the addition of benzyl chloride up to completion of the

reaction. Distill off DEE and maintain for few hours and then cool to room temperature.

Check the sample and unload the material into the containers under nitrogen

atmosphere.Check the Product and unload the material into the containers under

Nitrogen atmosphere.

BENZYL MAGNESIUM CHLORIDE

Route of synthesis:

Stage-1:

Mg

Magnesium

24.31

+

Benzyl chloride

Cl

C7H7Cl

126.58

MgCl

Benzylmagnesium chloride

C7H7ClMg

150.89

THF




Flow Chart:

MagnesiumBenzyl chlorideDiethyl etherTetrahydrofuran

Diethyl ether RecTHF Rec

Stage-1



Material Balance:

Material Balance of Benzyl Magnesium Chloride Stage-1

Batch Size: 1000.0Kgs Name of the input Quantity

in Kg Name of the out put Quantity

in Kg

Magnesium 160.00 Benzyl magnesium chloride in THF Solution

2056.00

Benzyl chloride 840.00 Diethyl ether Recovery 732.00 Diethyl ether 770.00 Diethyl ether Loss 38.00 Tetrahydrofuran 1100.00 Tetrahydrofuran Loss 44.00 Total 2870.00 Total 2870.00



2. BUTYL MAGNESIUM CHLORIDE

Process Description

Stage-1


Charge THF and start stirring. Raise the reactor temperature up to required

temperature. Start and continue the addition of butyl chloride up to completion of the

reaction. Maintain for few hours and cool to room temperature. Check the Products and

unload the material into the containers under Nitrogen atmosphere.

BUTYL MAGNESIUM CHLORIDE

Route of Synthesis

Stage-1

Mg

Magnesium

24.31

+

Butyl chloride

Nitrogen

Butyl Magnesium ChlorideTHF

CH3ClMg

ClCH3

116.87

C4H9MgClC4H9Cl

92.57




Flow Chart

Stage-1 THF RecMagnesium MetalButyl ChlorideTHF



Material Balance:

Material Balance of Butyl Magnesium Chloride Stage-1

Batch Size: 1000.0 Kgs Name of the input Quantity


in Kg

Magnesium Metal 210.00 Butyl Magnesium Chloride in THF Solution

1768.00

Butyl Chloride 790.00 THF Loss 40.00 THF 805.00 Total 1808.00 Total 1808.00



3. DOMPERIDONE

Process Description: Stage-1

N-carbethoxy-4-piperidone is reacted with Hydrogen and Ammonia in the presence of

Raney nickel as catalyst and Methanol as solvent media to give stage-1 as product.

Stage-2

Stage-1 reacts with 2, 5-Dichloro nitrobenzene & Sodium Carbonate in presence of

Methanol as a solvent media to give Stage-2 as product.

Stage-3

Stage-2 reacts with Hydrogen in presence of Raney Nickel as catalyst and Toluene

as solvent media to give Stage-3 as product.

Stage-4

Stage-3 reacts with Urea in the presence of Sodium Hydroxide as a solvent media to

give Stage-4 as product.

Stage-5

Stage-4 undergoes hydrolysis with Sodium Hydroxide to give Stage-5 as product.

Stage-6

Stage-5 reacts with 1-(3-chloropropyl)-1, 3-dihydro-2H-benzimedazole-2-one and

Sodium Carbonate in the presence of Methyl Isobutyl Ketone as solvent media to give

Domperidone as product.



DOMPERIDONE

Route of synthesis:

Stage-1

N-Carbethoxy-4-piperidone

N

O

O O CH3

C8H13NO3

171.19

+ H2

Hydrogen

2.00

+ NH3

Ammonia

17.03

+ H2O

4-Amino-piperidine-1-carboxylic acid ethyl ester

N

NH2

O O CH3

18.00

C8H16N2O2

172.22

Raney Nickel

Stage-2

4-Amino-piperidine-1-carboxylic acid ethyl ester

N

NH2

O O CH3

C8H16N2O2

172.22

+

2,5-Dichloro Nitrobenzene

Cl

Cl

NO2

C6H3Cl2NO2

192.00

+ 1/2 Na2CO3

Sodium carbonate

1/2X105.98=52.99

N

HN

O O CH3

NO2

Cl

4-(4-Chloro-2-nitro-phenylamino)-piperidine-1-carboxylic acid ethyl ester

+

C14H18ClN3O4

327.76

NaCl

Sodium chloride

58.44

+ 1/2 H2O1/2 CO2

Carbon dioxide1/2X44=22.00

+

1/2X18=9.00

Methanol



Stage-3

N

HN

O O CH3

NO2

Cl

4-(4-Chloro-2-nitro-phenylamino)-piperidine-1-carboxylic acid ethyl ester

C14H18ClN3O4

327.76

+ 3 H2

3X2=6.00

Hydrogen

N

HN

O O CH3

NH2

Cl

4-(2-Amino-4-chloro-phenylamino)-piperidine-1-carboxylic acid ethyl ester

C14H20ClN3O2

297.78

+ 2H2O

2X18=36.00

Raney Nickel

Toluene

Stage-4

N

HN

O O CH3

NH2

Cl

4-(2-Amino-4-chloro-phenylamino)-piperidine-1-carboxylic acid ethyl ester

C14H20ClN3O2

297.78

+

Urea

H2N

O

NH2

CH4N2O

60.05

N

O O CH3

N

HNCl

O

4-(5-Chloro-2-oxo-2,3-dihydro-enzoimidazol-1-yl)-piperidine-1-

carboxylic acid ethyl ester

C15H18ClN3O3

323.77

+ 2NH3

2X17.03=34.06

Ammonia

NaOH



Stage-5

N

O O CH3

N

HNCl

O

C15H18ClN3O3

323.77

+

Sodium hydroxide

NaOH

40.00

4-(5-Chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester

NH

N

HNCl

O

5-Chloro-1-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one

+ C2H5ONa

Sodium ethoxide

68.05

+ CO2

Carbon dioxide

44.00

C12H14ClN3O

251.71



Stage-6

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

+ 1/2Na2CO3

Sodium carbonate

NH

N

ON

NH

N

O Cl

425.91

Domperidone

C22H24ClN5O2

+ NaCl

Sodium chloride

58.44

+ 1/2 H2O +1/2 CO2

Carbon dioxideWater

1/2X44=22.001/2X18=9.00

1/2X105.98=52.99

MIBK



DOMPERIDONE

Flow Chart:

Stage-170.0 Kg

ProductMethanol Rec

Effluent water

Stage-295.0 Kg

ProductMethanol Rec

Effluent water

Stage-375.0 Kg

ProductToluene Rec

Effluent water

Stage-12,5-Dichloro NitrobenzeneSodium CarbonateMethanol

Stage-467.0 Kg

ProductAmmonia

Effluent water

Stage-545.0 Kg

ProductCarbon Dioxide

Effluent water

Stage-650.0 Kg

Product

Sodium chlorideCO2

Effluent water

DOMPERIDONE

N-Carbethoxy-4-piperidoneAmmonia gasMethanolRaney NickelHydrogen

Stage-2HydrogenRaney NickelToluene

Stage-3UreaSodium Hydroxide (48%)

Stage-4Sodium Hydroxide

Stage-51-(3-Chloropropyl)-1,3-dihydro2H-benzimedazole-2-oneSodium CarbonateMethyl Isobutyl Ketone



DOMPERIDONE

Material Balance:

Material Balance of Domperidone Stage-1

Batch Size:50Kg Name of the input Quantity


in Kg N-Carbethoxy-4-piperidone 80.00 Stage-1 70.00 Ammonia gas 28.00 Methanol Recovery 283.00 Methanol 300.00 Methanol Loss 15.00 Raney Nickel 20.00 Spent Raney Nickel 20.00 Hydrogen 5.00 Generated water 8.40 Process Emission 24.00 (Ammonia-20,Hydrogen-4) Organic Residue 12.60 (Organic Impurities-10.6,Methanol-

2)

Total 433.00 Total 433.00




in Kg Stage-1 70.00 Stage-2 95.00 2,5-Dichloro Nitrobenzene 78.00 Methanol Recovery 470.00 Sodium Carbonate 30.00 Methanol Loss 25.00 Methanol 500.00 Effluent Water 538.85 Water 500.00 (Water-500,generated water-

3.65,Sodium chloride-23.7,Sodium carbonate-8.5,Methanol-3)

Process Emission 8.93 (Carbon dioxide) Organic Residue 40.22 (Organic Impurities-38.22,

Methanol-2)

Total 1178.00 Total 1178.00






in Kg Stage-2 95.00 Stage-3 75.00 Hydrogen 5.00 Toluene Recovery 330.00 Raney Nickel 10.00 Toluene Loss 17.00 Toluene 350.00 Raney Nickel Reuse 10.00 Water 400.00 Effluent Water 411.43 (Water-400,generated water-10.43,

Toluene-1)

Process Emission 3.27 (Hydrogen) Organic Residue 13.30 (Organic Impurities-11.3,Toluene-2) Total 860.00 Total 860.00




in Kg Stage-3 75.00 Stage-4 67.00 Urea 20.00 Effluent Water 664.90 Sodium Hydroxide (48%) 60.00 (Water-600,Urea-4.9,Sodium

hydroxide-28.8,water from sodium hydroxide-31.2)

Water 600.00 Process Emission 8.57 (Ammonia) Organic Residue 14.53 Total 755.00 Total 755.00






in Kg Stage-4 67.00 Stage-5 45.00 Sodium Hydroxide 15.00 Effluent Water 420.70 Water 400.00 (Water-400,Sodium hydroxide-6.7,

Sodium ethoxide-14)

Process Emission 9.10 (Carbon dioxide) Organic Residue 7.20 Total 482.00 Total 482.00




in Kg Stage-5 45.00 Domperidone 50.00 1-(3-Chloropropyl)-1,3-dihydro-2H-benzimedazole-2-one

40.00 Methyl Isobutyl Ketone Recovery 1135.00

Sodium Carbonate 20.00 Methyl Isobutyl Ketone Loss 60.00 Methyl Isobutyl Ketone 1200.00 Effluent Water 424.50 Water 400.00 (Water-400,generated water-

1.6,Sodium chloride-10.4,Sodium carbonate-10.5,MIBK-2)

Process Emission 3.93 (Carbon Dioxide) Organic Residue 31.57 (Organic Impurities-28.57,MIBK-3) Total 1705.00 Total 1705.00



4. ESCITALOPRAM OXALATE


Stage-1

5-Bromo phthalide reacts with P-Fluoro Magnesium chloride in the presence of Toluene as a solvent media to give stage-1 as product.

Stage-2

Stage-1 reacts with HBr in the presence of Toluene as a solvent media to give stage-2 as product.

Stage-3

Stage-2 reacts with MPR as a resoluting agent in the presence of Toluene as a solvent media to give stage-3 as product.

Stage-4

Stage-3 undergoes resolution in the presence of Toluene as a solvent media to give stage-4 as product.

Stage-5

Stage-4 undergoes cyclisation in the presence of Toluene as a solvent media to give stage-5 as product.

Stage-6

Stage-5 reacts with Oxalic acid in the presence of Toluene as a solvent media to give stage-6 as product.

Stage-7

Stage-6 reacts with cuprous cyanide in the presence of Toluene as a solvent media to give stage-7 as product.

Stage-8

Stage-7 reacts with Oxalic acid in the presence of Toluene as a solvent media to give Escitalopram Oxalate as product.



ESCITALOPRAM OXALATE

Route of synthesis:

Stage-1: Br

O

O

5-Bromo pthalide

C8H5BrO2

213.02

+

P-Fluoromagnesium bromide

F

MgBr

199.30

Dimethyl amino magnesium chloride

NH3C

H3CMgCl+

145.91

OH

OHN

CH3

CH3

F

396.29

+ Mg(Br)OH +

121.21

Mg(Cl)OH

76.76

C6H4BrFMg C5H12ClMgN

+ 3H2O

3X18=54.00

Toluene

4-Dimethylamino-1-(4-fluoro-phenyl)-1-(2-hydroxymethyl-

phenyl)-butan-1-olC19H23BrFNO2

Magnesium hydroxy bromide

Magnesium hydroxy chloride

Br



Stage-2:

OH

OHN

CH3

CH3

F

396.29


phenyl)-butan-1-olC19H23BrFNO2

Br

+ HBr

80.91

Hydrobromic acid

OH

OHN

CH3

CH3

F

Br

HBr


phenyl)-butan-1-ol

C19H23BrFNO2.HBr

477.20

Toluene

Stage-3:

OHOH

NCH3

CH3

F

Br

HBr


phenyl)-butan-1-ol Hydrobromide

C19H23BrFNO2.HBr

477.20

+O

OO OH

O

OO OH

CH3

H3C

MPR

C20H18O8

386.35

Toluene

OHOH

NCH3

CH3

F

Br

O

OO OH

O

OO OH

CH3

H3C

C19H23BrFNO2.C20H18O8

782.64

+ HBr

80.91

Hydrobromic acid1-(4-Bromo-2-hydroxymethyl-phenyl)-4-dimethylamino

-1-(4-fluoro-phenyl)-butan-1-ol with (+)/(-) MPR Salt



Stage-4:

OHOH

NCH3

CH3

F

Br

O

OO OH

O

OO OH

CH3

H3C

C19H23BrFNO2.C20H18O8

782.64

1-(4-Bromo-2-hydroxymethyl-phenyl)-4-dimethylamino-1-(4-fluoro-phenyl)-butan-1-ol with (+)/(-) MPR Salt

Toluene

OH

OHNCH3

CH3

F

Br

1-(4-Bromo-2-hydroxymethyl-phenyl)-4-dimethylamino-1-(4-fluoro-phenyl)-butan-1-ol

C19H23BrFNO2

396.29

O

OO OH

O

OO OH

CH3

H3C

C20H18O8

386.35

MPR

+



Stage-5:

OHOH

NCH3

CH3

F

Br

1-(4-Bromo-2-hydroxymethyl-phenyl)-4-dimethylamino-1-(4-fluoro-phenyl)-butan-1-ol

C19H23BrFNO2

396.29

NCH3

CH3

F

BrO

{3-[5-Bromo-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-1-yl]-propyl}-dimethyl-amine

C19H21BrFNO

378.27

+ H2O

18.00

Toluene

Stage-6:

NCH3

CH3

F

BrO

{3-[5-Bromo-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-1-yl]-propyl}-dimethyl-amine

C19H21BrFNO

378.27

+

Oxalic acid

O OH

OHO

C2H2O4

90.03

NCH3

CH3

F

BrO

O OH

OHO

{3-[5-Bromo-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-1-yl]-propyl}-dimethyl-amine salt of Oxalic acid

C19H21BrFNO.C2H2O4

474.36

Toluene



Stage-7:

NCH3

CH3

F

BrO

O OH

OHO

{3-[5-Bromo-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-1-yl]-propyl}-dimethyl-amine salt of Oxalic acid

C19H21BrFNO.C2H2O4

468.31

+ CuCN

89.56

Cuprous cyanide

NCH3

CH3

F

NCO

{3-[5-Cyano-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-1-yl]-propyl}-dimethyl-amine

C20H21FN2O

324.39

+ CuBr +

Oxalic acid

O OH

OHO

Cuprous bromide

143.45 90.03

Toluene



Stage-8:

NCH3

CH3

F

NCO

{3-[5-Cyano-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-1-yl]-propyl}-dimethyl-amine

C20H21FN2O

324.39

+

Oxalic acid

O OH

OHO

90.03

C2H2O4

Toluene

NCH3

CH3

F

NCO

O OH

OHO

{3-[5-Cyano-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-1-yl]-propyl}-dimethyl-amine salt of Oxalic acid

C20H21FN2O.C2H2O4

414.42



Stage-9

NCH3

CH3

F

NCO

O OH

OHO

C20H21FN2O.C2H2O4

414.42

Esitolopram oxalate

IPA

NCH3

CH3

F

NCO

O OH

OHO

C20H21FN2O.C2H2O4

414.42

Esitolopram oxalate




Flow Chart:

Stage-1

Stage-2

Stage-3

Stage-4

Stage-5

BromophthalideFluorobromobenzeneDimethyl amino propylmagnesium chlorideMagnesium turnings

Effluent water

Stage-1Hydrobromic acidActivated carbonToluene

Toluene RecEffluent water

Stage-2MPRActivated carbonIPAToluene

IPA RecToluene RecEffluent water

Stage-3Sodium hydroxideSodium sulfateToluene

Toluene RecEffluent water

Stage-4Methane sulfonyl chlorideTriethylamineSodium sulfateToluene

Acetone RecEffluent water



Stage-6

Stage-7

Stage-8

Stage-9

Stage-5Oxalic acidAcetone

Acetone Rec

Stage-6Sodium hydroxideCopper cyanideEthylene di amineDMFToluene

DMF RecToluene Rec

Stage-7Oxalic acidTolueneIPA

IPA RecToluene RecEffluent water

Stage-8IPAActivated carbon

IPA Rec





Material Balance:

Material Balance of Escitalopram oxalate Stage-1

Batch Size: 100 Kgs Name of the input Quantity


in Kg Bromo phthalide 110.00 Stage-1 200.00 Fluoro bromo benzene 103.00 Toluene Recovery 474.00 Dimethyl amino propyl magnesium chloride

76.00 Toluene Loss 25.00

Magnesium turnings 28.00 THF Recovery 949.00 Acetic acid 87.00 THF Loss 50.00 Iodine 3.00 Effluent water 883.80 Ammonia Liq 90.00 (Water-572.2, Magnesium hydroxyl

bromide-62.6,Magnesium hydroxyl chloride-40,Magnesium turnings-28,Acetic acid-87, Ammonia-9,Water from ammonia-81,Iodine-3, THF-1)

Activated carbon 4.00 Spent carbon 4.00 Toluene 500.00 Organic Residue 15.20 Tetrahydrofuran 1000.00 (Organic Impurites-14.2,Toluene-

1)

Water 600.00 Total 2601.00 Total 2601.00






in Kg Stage-1 200.00 Stage-2 225.00 Hydro bromic acid 41.00 Toluene Recovery 333.00 Activated carbon 5.00 Toluene Loss 17.00 Toluene 350.00 Effluent water 601.00 Water 600.00 (Water-600,Toluene-1) 0 Spent carbon 5.00 Organic Residue 15.00 Total 1196.00 Total 1196.00




in Kg Stage-2 225.00 Stage-3 350.00 MPR 173.00 Toluene Recovery 1424.00 Caustic flakes 38.30 Toluene Loss 75.00 Sodium sulfate 62.00 IPA Recovery 949.00 Activated carbon 7.30 IPA Loss 50.00 IPA 1000.00 Effluent water 677.34 Toluene 1500.00 (Water-600,Generated water-

8.47,Sodium bromide-48.4,Sodium hydroxide-19.47,Toluene-1)

Water 600.00 Inorganic sold waste 62.00 (Sodium sulfate) Organic solid waste 10.96 (Organic Impurities-9.96,IPA-1) Spent carbon 7.30 Total 3605.60 Total 3605.60






in Kg Stage-3 350.00 Stage-4 165.00 Sodium hydroxide 10.00 Toluene Recovery 6173.00 Sodium sulfate 100.00 Toluene Loss 325.00 Toluene 6500.00 Effluent water 411.00 Water 400.00 (Water-400,Sodium hydroxide-

10,Toluene-1)

Inorganic solid waste 100.00 (Sodium sulfate) MPR Reagent Reuse 173.00 Organic Solid waste 13.00 (Organic Impurities-12,Toluene-1) Total 7360.00 Total 7360.00




in Kg Stage-4 165.00 Stage-5 150.00 Methane sulfonyl chloride 50.00 Toluene Recovery 6173.00 Triethylamine 15.00 Toluene Loss 325.00 Sodium chloride 20.00 Effluent water 493.50 Sodium sulfate 100.00 (Water-400,Generated water-7.5,

Methane sulfonyl chloride-50, Sodium chloride-20,Triethyl amine-15,Toluene-1)

Toluene 6500.00 Inorganic solid waste 100.00 Water 400.00 (Sodium sulfate) Organic Residue 8.50 (Organic Impurities-7.5,Toluene-1) Total 7250.00 Total 7250.00






in Kg Stage-5 150.00 Stage-6 180.00 Oxalic acid 40.00 Acetone Recovery 1095.00 Acetone 1152.00 Acetone Loss 56.00 Organic Residue 11.00 (Organic Impurities-10,Acetone-1) Total 1342.00 Total 1342.00




in Kg Stage-6 180.00 Stage-7 120.00 Copper cyanide 45.00 Toluene Recovery 2660.00 Copper iodide 57.00 Toluene Loss 139.00 Ethylene di amine 267.00 DMF Recovery 2173.00 DMF 2288.00 DMF Loss 114.00 Toluene 2800.00 Ethylene di amine Recovery 254.00 Water 300.00 Ethylene di amine Loss 13.00 Effluent water 458.00 (Water-300,Cuprous bromide-

56,Oxalic acid-44,Copper iodide-57,DMF-1)

Organic Residue 6.00 (Organic Impurities-5,Toluene-1) Total 5937.00 Total 5937.00






in Kg Stage-7 120.00 Stage-8 129.00 Oxalic acid 34.00 Toluene Recovery 2659.00 Ammonia Liquid 114.00 Toluene Loss 140.00 Acetic acid 34.00 Isopropyl ether Recovery 228.00 Activated carbon 50.00 Isopropyl ether Loss 12.00 Hyflow 10.00 Acetone Recovery 542.00 Toluene 2800.00 Acetone Loss 28.00 Isopropyl ether 240.00 Effluent water 550.00 Acetone 572.00 (Water-400,Acetic acid-34,

Ammonia-11.4,Water from ammonia-102.6, Toluene-1, Acetone-1)

Water 400.00 Spent carbon &Hyflow 60.00 Organic Residue 26.00 (Organic Impurities-25,Acetone-1) Total 4374.00 Total 4374.00




in Kg Stage-8 129.00 Escitalopram oxalate 100.00 IPA 3200.00 IPA Recovery 3039.00 Activated carbon 14.00 IPA Loss 160.00 Spent carbon 14.00 Organic Residue 30.00 (Organic Impurities-29,IPA-1) Total 3343.00 Total 3343.00



5. ESOMEPRAZOLE MAGNESIUM TRIHYDRATE

Process

Description:

Stage-1

5-Methoxy-2-[(4-Methoxy-3,5-Dimethyl-2-pyridinyl) Methyl Thio]-1H-

Benzimidazole reacts with Cumin hydroperoxide and Potassium hydroxide in the

presence of Toluene as a solvent media to give stage-1 as product. Stage-2

Stage-1 undergoes hydrolysis with Magnesium sulfate in the presence of Toluene

as a solvent media to give Esomepraszole Magnesium Trihydrate as product.



ESOMEPRAZOLE MAGNESIUM TRIHYDRATE

Route of synthesis:

Stage-1:

OCH3

H3C CH3

N OCH3

CH3 OH

H3C O

Toluene

N C S +

H2 N

H

+ KOH

5-Methoxy-2-[(4-methoxy-3, 5-dimethyl-pyridin

-2-ylmethyl Thio]-1H -Benzoimidazole

C17H19N3O2S

329.41

OCH3

H3C CH3

Cumin hydroperoxide

C9H12O2

152.19

H3C

Potassium hydroxide

56.10

CH3

OH

O N

N C S H2

N

K+

OCH3

H2O +

Esomeprazole potassium salt.Monohydrate Cumin hydroxide

C17H20KN3O4S C9H12O 136.19

401.52



Stage-2:

OCH3

H3C CH3

O

2

N OCH3

N C S H2

N

K+

H2O + MgSO4 + H2O

Esomeprazole potassium salt.Monohydrate

C17H20KN3O4S

2X401.52=803.04

Magnesium sulfate

120.36

18.00

OCH3

H3C CH3

O

N OCH3

Mg 3H2O + K2SO4

N C S H2

N 2

Esomeprazole Magnesium Tri Hydrate

C17H18N3O3S.Mg3H2O

767.15

Potassium sulfate

174.25



ESOMEPRAZOLE MAGNESIUM TRIHYDRATE Flow Chart:

Omeprazole sulfide Cumin hydroperoxide Potassium hydroxide Methanol

Stage-1

Methanol Rec

Stage-1 Magnesium sulfate Water

Stage-2

Effluent Water

ESOMEPRAZOLE MAGNESIUM



ESOMEPRAZOLE MAGNESIUM TRIHYDRATE

Material Balance:

Material Balance of Esomeprazole Magnesium trihydrate Stage-1

Batch Size: 100 Kgs Name of the input Quantity in

Kg Name of the out put Quantity in

Kg Name of the input Quantity


In Kg Omeprazole sulfide 88.00 Stage-1 107.00 Cumin hydro peroxide 41.00 Toluene Recovery 305.00 Potassium hydroxide 15.20 Toluene loss 15.00 DET 11.30 Methanol Recovery 95.00 Titanium isopropoxide 2.50 Methanol Loss 5.00 NEDIPA 4.50 NEDIPA Loss 4.50 Toluene 320.00 Organic Residue 51.00 Methanol 100.00 (DET-11.3,Titanium

isopropoxide-2.5,Cumin hydroxide-37.2,)


Material Balance of Esomeprazole Magnesium trihydrate Stage-2

Batch Size: 100 Kgs Name of the input Quantity in

Kg Name of the out put Quantity in

Kg Name of the input Quantity in

Kg Name of the out put Quantity

In Kg Stage-1 107.00 Esomeprazole Magnesium

trihydrate 100.00

Magnesium sulfate 16.00 Effluent water 980.80 Water 960.00 (Water-957.6,Potassium

sulfate-23.2)

Organic Residue 2.20 Total 1083.00 Total 1083.00



6. ETHYL MAGNESIUM CHLORIDE


Stage-1

Magnesium metal is charged into a clean and dry reactor under Nitrogen purging,


temperature. Start and continue the addition of ethyl chloride up to completion of

the reaction. Maintain few hours and cool to room temperature. Check sample and

unload the material into containers under Nitrogen atmosphere.

ETHYL MAGNESIUM CHLORIDE

Route of Synthesis:

Stage-1:

Mg +

Magnesium

24.31 C2H5MgCl

Ethyl Magnesium Chloride

88.82

THFH3C Cl

64.51

Ethyl Chloride

H3C MgCl




Flowchart:

Stage-1


Ethyl ChlorideMg turningsTHF

THF Recovery


Material Balance:

Material Balance of Ethyl Magnesium Chloride Stage-1



in Kg

Ethyl Chloride 724.00 Ethyl Magnesium Chloride in THF Solution

2425.00

Mg turnings 276.00 THF Loss 75.00 THF 1500.00 Total 2500.00 Total 2500.00



7. LINEZOLID


Stage-1:

N-[3-pthalimido-2R-Hydroxy propyl]-3-(fluoro-4-morpholinyl) aniline is treated with

carbonyl diimidazole, Hydrazine hydrate and acetic anhydride in the presence of

MDC and Methanol to give Linezolid as product.



LINEZOLID Route of Synthesis: Stage-1

O N

F

NH

N

OH

O

O

2-[3-(3-Fluoro-4-morpholin-4-yl-phenylamino)-2-hydroxy-propyl]-isoindole-1,3-dione

C21H22FN3O4

399.42

+

Carbonyl diimidazole

O

N

HNNH

N

C7H6N4O

162.15

+

Hydrazine hydrate

H2NNH2H

OH

H6N2O

50.06

+

Acetic anhydride

OO

O

C4H6O3

102.09

MDC

O N

F

NO

O

HN CH3

O

Linezolid

C16H20FN3O4

337.35

+

Imidazole

N

HN

2

C3H4N2

2X68.08=136.16

+ CH3COOH

60.0

+

Phthalazine -1,4-diol

N

N

OH

OH

C8H6N2O2

162.15

+ H2O

18.0

LINEZOLID



Flow Chart:

N-[3-Phthalimido-2R-hydroxypropyl-3-fluoro-4-morpholinyl anilineCarbonyl diimidazoleHydrazine HydrateMethanol

Stage-1 Methanol Rec

LINEZOLID

LINEZOLID

Material Balance:

Material balance of Linezolid Stage-1

Batch Size:90.0 Kg Name of the input Quantity


In Kg N-[3-Phthalimido-2R-hydroxypropyl-3-fluoro-4-morpholinyl aniline

110.00 Linezolid 90.00

Carbonyl di imidazole 43.25 Methanol Recovery 710.00 Hydrazine Hydrate 13.35 Methanol Loss 37.00 Acetic anhydride 27.23 MDC Recovery 2548.00 Methanol 753.00 MDC Loss 134.00 MDC 2682.00 Ethyl acetate Recovery 765.00 Activated carbon 10.80 Ethyl acetate Loss 40.00 Ethyl acetate 805.00 Acetone Recovery 1471.00 Acetone 1548.00 Acetone Loss 77.00 Water 1422.00 Effluent water 1523.38 (Water-1422,Generated water-

4.8,Acetic acid-16,Phthalazine-1,4-diol-43.25,Methanol-1,Imidazole-36.33)

Spent carbon 10.80 Organic Residue 8.45 (Organic Impurities-

3.45,Methanol-5)

Total 7414.63 Total 7414.63



8. LOPERAMIDE HYDROCHLORIDE


Stage-1:

N-(3,3-diphenyldihydrofuran-2(3H)-ylidene)-N-methylmethanaminium bromide is

reacted with 4-(Chloro phenyl) - Piperidine –4-ol in presence of Potassium

carbonate(K2CO3), Potassium iodide(KI), Potassium hydroxide (KOH) acetone,

Toluene ,HCl & Water to get Stage-1 compound.

Stage-2

Stage I is reacted with Methanolic HCl and then it is purified in presence of Acetone,

Methanol & Activated carbon to get Loperamide HCl (Pharama)



LOPERAMIDE HYDROCHLORIDE

Route of Synthesis

Stage-1:

N-(3,3-diphenyldihydrofuran-2(3H)-ylidene)-N-methylm

ethanaminium bromide

N+

O

Br-

4-(Chloro phenyl) - Piperidine -4-ol

HN

OH Cl

4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-

diphenylbutanamide

++ 1/2 K2CO3

PotassiumCarboante

ON

N

OH

Cl

C18H20BrNO

346.26

C11H14ClNO

211.69

1/2X138.21=69.1

C29H33ClN2O2477.04

+ KBr + 1/2 CO2 + 1/2H2O

119.0 1/2X44=22.0 1/2X18=9.0

Acetone / KI



Stage-2:

4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]- N,N-dimethyl-2,2-diphenylbutanamide

O

NN

OHCl

C29H33ClN2O2

477.04

O

NN

OHCl

4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-

diphenylbutanamide Hydrochloride

C29H34Cl2N2O2

513.50

+ HCl

Hydrochloric Acid

36.46

Methanol

Carbon

HCl




Flow Chart

Stage-1

Stage-2

N-[(2Z)-3-(diphenylmethyl)dihydrafuran-2(3H)-ylidene]methanamine4-(Chloro phenyl)-Piperidine-4-ol Potassium carbonateAcetone

Acetone RecEffluent water

Stage-1MethanolAcetoneMethanolic HClActivated Carbon

Methanol RecAcetone RecSpent carbon





Material Balance

Material Balance of Loperamide Hydrochloride Stage-1

BatchSize:180 Kg Name of the input Quantity


in Kg N-[(2Z)-3-(diphenylmethyl)dihydrafuran-2(3H)-ylidene]methanamine

122.00 Stage-1 168.00

4-(Chloro phenyl)-Piperidine-4-ol 75.00 Acetone Recovery 563.00 Potassium carbonate 25.00 Acetone Loss 30.00 Potassium Iodide 1.00 Effluent Water 3051.11 Acetone 600.00 (Water-3000,generated water-

3.19,Potassium bromide-41.92, Acetone-5 , Potassium Iodide-1

Water 3000.00 Process Emission 7.96 (Carbon dioxide) Organic Residue 2.93 (Organic Impurities-0.93,

Acetone-2)

Total 3823.00 Total 3823.00



Material Balance of Loperamide Hydrochloride Stage-2

BatchSize:180Kg Name of the input Quantity


in Kg Stage-1 168.00 Loperamide Hydrochloride 180.00 Methanol 600.00 Methanol Recovery 677.50 Acetone 300.00 Methanol Loss 30.00 Methanolic HCl (10%) 125.00 Acetone Recovery 280.00 Activated Carbon 20.00 Acetone Loss 20.00 Spent Carbon 20.00 Organic Residue 5.50 (Organic Impurities-0.5,

Methanol-5)

Total 1213.00 Total 1213.00



9. MAGNESIUM TERTIARY BUTOXIDE

Process Description

Stage-1

2 moles of Methyl Magnesium Chloride in THF are reacted under certain conditions

to form Di methyl Magnesium and Magnesium Chloride.

Stage-2

Di methyl Magnesium in THF is reacted with Tertiary Butanol to get Magnesium

Tertiary Butoxide. The Magnesium Tertiary Butoxide solution in THF is taken into a

dryer and THF is recovered and used in next batches. The dried product is packed in

polythene bags and kept in MS drums.



MAGNESIUM TERTIARY BUTOXIDE

Route of Synthesis

Stage-1

2 CH3MgCl

Methl magnesium chloride

2X74.79=149.58

THF(CH3)2Mg

Di MethylMagnesium

54.37

+ MgCl2

Magnesium Chloride

95.21

Stage-2

THF(CH3)2Mg

Dimethyl Magnesium

54.37

+

Tert Butanol

CH3

H3C

CH3

OH2

2X74.12=148.24

C4H9OH

Magnesium Tertiary Butoxide

(C4H9O)2Mg

C8H18MgO2

170.53

+ 2 CH4

Methane gas

2X16.04=32.08




Flow Chart

Stage-1

Stage-2

Methyl magnesium ChlorideTHF

THF RecMgCl2(Byproduct)

Stage-1Tert-Butanol

Methane gasTert-Butanol Rec



Material Balance:

Material Balance of Magnesium Tertiary Butoxide Stage-1

Batch Size:200.0Kgs Name of the input Quantity


in Kg Methyl Magnsium Chloride 214.00 Stage-1+ THF 1400.00 THF 1400.00 THF Loss 70.00 By-product 144.00 (Magnesium chloride-144) Total 1614.00 Total 1614.00



Material Balance of Magnesium Tertiary Butoxide Stage-2



in Kg

Stage-1 + THF 1369.30 Magnesium Tertiary Butoxide in THF Solution

1528.00

Tert-Butanol 200.00 Process Emission 41.30 (Methane gas-41.30) Total 1569.30 Total 1569.30



10. METFORMIN HYDROCHLORIDE

Process Description

Dimethylamine hydrochloride reacts with Dicyanodiamide in the presence of Xylene

and Water Solvent media to produce aqueous layer containing Metformin

Hydrochloride which is purified with Activated carbon in the presence of Methanol

Solvent media to produce Metformin Hydrochloride.

METFORMIN HYDROCHLORIDE

Route of Synthesis:

Stage-1:

HN

CH3H3C

C2H8NCl

81.58

+ H2N NH

CN

NH

N-Cyanoguanidine

C2H4N4

84.08

Dimethyl amine Hydrochloride

HCl

NH3C

CH3

HN NH2

NH NH

HCl

Metformin Hydrochloride

C4H12N5Cl

165.66

Xylene




Flow Chart:

Stage - 1

Dimethylamine HclN-Cyano guanidineXyleneMethanol

Xylene RecoveryMethanol Recovery

Metformin Hydrochloride


Material Balance:

Material Balance of Metformin Hydrochloride Stage-1

Batch Size: 250Kg Name of the input Quantity


in Kg Dimethyl amine Hcl 126.00 Metformin Hydrochloride 250.00 N-Cyano guanidine 130.00 Xylene Recovery 285.00 Xylene 300.00 Xylene Loss 15.00 Activated carbon 2.00 Methanol Recovery 90.00 Hyflo 1.00 Methanol Loss 5.00 Methanol 100.00 Effluent water 324.00 Water 320.00 (Water-320,Methanol-1,Dimethyl

Amine Hydrochloride-3)

Spent carbon + Hyflo 2.00 Organic Residue 8.00 (Organic Impurities-4,Methanol-4) Total 979.00 Total 979.00



11. METHYL MAGNESIUM CHLORIDE

Process Description

Stage-1



temperature. Start and continue the addition of methyl chloride up to completion of

the reaction. Maintain for few hours and cool to room temperature. Check Product

and unload the material into the containers under nitrogen atmosphere.

METHYL MAGNESIUM CHLORIDE

Route of Synthesis

Stage-1

Mg

Magnesium

24.31

+ CH3Cl

Methyl chloride

Nitrogen

50.49

CH3MgCl

Methyl Magnesium Chloride

74.79

THF




Flow Chart

Stage-1 THF RecMagnesium MetalMethyl ChlorideTHF



Material Balance:

Material Balance of Methyl Magnesium Chloride Stage-1



in Kg

Magnesium Metal 974.00 Methyl Magnesium Chloride in THF Solution

4156.50

Methyl Chloride 2026.00 THF Loss 113.50 THF 1270.00 Total 4270.00 Total 4270.00



12. N, N-DIMETHYL PROPYL MAGNESIUM CHLORIDE

Process Description Stage-1 N, N-Dimethyl proyl amino chloride reacts with magnesium in presence of THF and

Toluene by addition of Catalytic amount of Iodine and EDB.

N, N-DIMETHYL PROPYL MAGNESIUM CHLORIDE

Route of Synthesis

Stage-1

Cl NCH3

CH3

(3-Chloro-propyl)-dimethyl-amine

C5H12ClN

+ Mg

24.31

121.61

I2 / EDB

THF/Toluene

ClMg NCH3

CH3

N,N-Dimethyl propylmagnesium chloride

C5H12ClMgN

145.91




Flow Chart

Stage-1


(3-Chloro-propyl)-dimethyl-amineMagnesium turningsEDBIodineTHFToluene

THF RecToluene Rec


Material Balance:

Material Balance of N,N-Dimethyl propyl Magnesium chloride Stage-1



in Kg (3-Chloro-propyl)-dimethyl-amine

417.00 N,N-Dimethyl propyl Magnesium chloride

500.00

Magnesium turnings 84.00 THF Recovery 950.00 EDB 1.00 THF Loss 50.00 Iodine 0.20 Toluene Recovery 950.00 THF 1000.00 Toluene Loss 50.00 Toluene 1000.00 Organic Residue 2.20 Total 2502.20 Total 2502.20



13. OMEPRAZOLE

Process Description

Stage-1

3, 5-Lutidine undergoes oxidation with Hydrogen peroxide initially in Acetic acid.

Then the reaction mass will be subjected to Nitration with Nitric acid and Sulphuric

acid mixture. Below is the equation.

Stage-2

Above stage compound on reaction with Sodium methoxide, Sodium Hydroxide and

Dimethyl sulphate in Methanol and water produces stage-2 product. Reaction takes

place as per the equation

Stage-3

A Stage-2 product on reaction with Thionyl chloride, APS and sodium hydroxide

produces stage-3 compound. Toluene is the solvent used in the process. Below is

the equation.

Stage-4

Stage-3 product on condensation with 5-Methoxy -2-Mercapto benzimidazole in

presence of C.S. Lye Produces stage-4.Toluene is the solvent medium

Stage-5

Above stage-4 compound on reaction with Hydrogen Peroxide produces stage-5

pharma. Methanol and Acetone are used in the process.



OMEPRAZOLE

Route of Synthesis:

Stage-1

N

3,5-LutidineC7H9N

107.15

+ H2O2

Hydrogen peroxide

34.01

+ HNO3

Nitric acid63.01

N

NO2

3,5-Dimethyl-4-nitro-pyridine N-Oxide

O

C7H8N2O3

168.15

Acetic acid+ 2H2O

2X18=36.0

.Stage-2

N

NO2

3,5-Dimethyl-4-nitro-pyridine N-Oxide

O

C7H8N2O3

168.15

+ CH3ONa

Sodium methoxide

54.02

+ 2NaOH

Sodium hydroxide

2X40=80.0

+ (CH3)2SO4

Dimethyl sulfate

126.13

Methanol

N

COOH

3,5-Dimethyl-isonicotinic acid N-Oxide

O

+ NaNO2

69.0

+ H2O

18.0

+ Na2SO4

142.04

+ CH3OH

32.0

C8H9NO3

167.16



Stage-3

N

COOH

3,5-Dimethyl-isonicotinic acid N-Oxide

O

C8H9NO3

167.16

+ SOCl2

Thionyl chloride

118.97

+ NH4OH

Ammonium hydroxide

35.05

Toluene N

ClO

3,5-Dimethyl-isonicotinoyl chloride N-Oxide

O

C8H8ClNO2

185.61

+ NH4Cl + H2O + SO2

53.49 18.0 64.06

Stage-4

N

ClO

3,5-Dimethyl-isonicotinoyl chloride N-Oxide

O

C8H8ClNO2

185.61

2-Mercapto-5-methoxy benzimidazole

N

HN

O

HS+

C8H8N2OS

180.23

+ NH4OH

Ammonium Hydroxide

35.05

Toluene

N

NH

O

S

N

CH3

H3C OCH3

5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethylsulfanyl)-

1H-benzoimidazoleC17H19N3O2S

329.42

+ NH4Cl + H2O

18.053.49



Stage-5

N

NH

O

S

N

CH3

H3C OCH3

5-Methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethylsulfanyl)-1H-benzoimidazole

C17H19N3O2S

329.42

+ H2O2

Hydrogen peroxide

34.01

Methanol

HN

N

S

O

N

O

O

Omeprazole

C17H19N3O3S

345.42

+ H2O

18.0



OMEPRAZOLE

Flow Chart:

Stage-147.3 Kg

Product

Effluent water

Stage-242.5 Kg

ProductMethanol Rec

Effluent water

Stage-352.40 Kg

ProductToluene Rec

Effluent water

Stage-1Sodium methoxideSodium hydroxideDimethyl sulphateMethanol

Stage-494.0 Kg

ProductToluene Rec

Effluent water

Stage-5100.0 Kg

ProductMethanol RecAcetone Rec

3,5-LutidineHydrogen PeroxideAcetic acid

Stage-2Thionyl ChlorideSodium hydroxideToluene

Stage-32-Mercapto-5-methoxy BenzimidazoleCS LyeToluene

Stage-4Hydrogen peroxideMethanolAcetone

Effluent water

OMEPRAZOLE



OMEPRAZOLE

Material Balance:

Material balance of Omeprazole Stage-1



in Kg 3,5-Lutidine 33.00 Stage-1 51.00 Hydrogen Peroxide 11.00 Effluent Water 411.14 Acetic acid 25.00 (Water-400,gen.water-

11.14) 0

Nitric acid 19.50 Acetic acid recovery 25.00 Water 400.00 Organic Residue 1.36 Total 488.50 Total 488.50




in Kg Stage-1 51.00 Stage-2 50.00 Sodium methoxide 16.40 Methanol Recovery 475.00 Sodium hydroxide 24.30 Methanol Loss 25.00 Dimethyl sulphate 38.30 Effluent Water 615.17 Methanol 500.00 (Water-600,gen.water-5.45,

Methanol-9.72) 0

Water 600.00 By-Product 64.06 (Sodium Sulphate-43.13,

Sodium nitrate-20.93) 0







in Kg Stage-2 50.00 Stage-3 55.00 Thionyl Chloride 36.00 Toluene Recovery 465.00 Ammonium hydroxide 11.00 Toluene Loss 25.00 Toluene 500.00 Effluent water 415.38 Water 400.00 (Water-400,gen.water-5.38

Toluene-10)

By-Product 16.80 (Ammonium chloride) Process Emission 19.38 (Sulphur dioxide) Organic Residue 0.44 Total 997.00 Total 997.00


Batch Size:100 Kg Name of the input Quantity


in Kg Stage-3 55.00 Stage-5 96.00 2-Mercapto-5-methoxy Benzimidazole

53.50 Toluene Recovery 470.00

Ammonium hydroxide 11.00 Toluene Loss 25.00 Toluene 500.00 Effluent Water 355.33 Water 350.00 (Water-350,Generated water-

5.33)

By-Product 16.80 (Ammonium chloride-16.8) Organic Residue 6.37 Total 969.50 Total 969.50



Material balance of Omeprazole Stage-5:Pharma

Batch Size:100 Kg Name of the input Quantity


in Kg Stage-4 96.00 Omeprazole 100.00 Hydrogen peroxide 12.00 Methanol Recovery 237.50 Methanol 250.00 Methanol Loss 12.50 Acetone 250.00 Acetone Recovery 237.50 Acetone Loss 12.50 Effluent water 5.25 (Generated Water) Organic Residue 2.75 Total 608.00 Total 608.00



14. PANTOPRAZOLE SODIUM

Process Description

Stage-1 Maltol and Dimethyl sulphate condense in Acetone solvent medium. Excess Dimethyl sulphate is removed by treating the reaction mass with Potassium Carbonate. Reaction takes place as per the below equation.

Stage-2 Stage-1 compound on treating with Liquor Ammonia solution stage-2 compound is formed. Reaction proceeds as per the below equation

Stage-3 Stage-2 compound on reaction with Phosphorous oxy chloride produces stage-3 compound. Further reaction is stopped by treating the reaction mass with water. Final product is extracted with MDC and after distilling out MDC compound is obtained. Below is the reaction scheme.

Stage-4 Stage-3 compound when reacts with Hydrogen peroxide in presence of Acetic acid, stage-4 compound is obtained. Methanol is the solvent employed.

Stage-5 Stage-4 compound on reaction with Methanol in sodium methoxide presence produces stage-5 compound. Execs Methanol is used. Below is the reaction

Stage-6 Above stage compound on reaction with Acetic anhydride produces an intermediate.MDC used as solvent. Product is precipitated with C.S. Flakes. Below is the reaction scheme.

Stage-7 Stage-6 compound when reacts with Sodium hydroxide MDC is used as solvent.

Stage-8 Stage-7 compound when reacts with Thionyl chloride an intermediate is formed.MDC is used as solvent. Product is crystallized in Methanol. Finally product is purified with Acetone.

Stage-9 When 2-Chloromethyl-3, 4-dimethoxy-pyridine Hydrochloride reacts with 5-diFluoro methoxy-2-mercapto-benzimidazole, in presence of Sodium hydroxide, product is formed. Methylene dichloride is the solvent.

Stage-10 Stage-9 is treated with Sodium hypochlorite in presence of Sodium hydroxide, to produce the Pantoprazole sodium .This is purified in Acetone. Methylene dichloride is used as solvent.



PANTOPRAZOLE SODIUM

Route of Synthesis:

Stage-1:

O

O

OH

CH3

Maltol

C6H6O3

2X126.11=252.22

Dimethyl sulphate

(CH3)2SO4

126.13

K2CO3

138.21

Acetone

O

O

OCH3

CH3

C7H8O3

2x140.14=280.28

K2SO4

174.26

CO2

44.0

+ + +

+ + H2O

18.0

2 2

3-Methoxy-2-methyl-pyran-4-one

Stage-2:

O

O

OCH3

CH3

C7H8O3

140.14

(NH4)2CO3

Ammonium carbonate

96.0

NH

O

OCH3

CH3

C7H9NO2139.15

+ + NH4OH + CO2 + H2O

35.0 44.0 18.03-Methoxy-2-methyl-pyran-4-one 3-Methoxy-2-methyl-

1H-pyridin-4-one

Stage-3:

NH

O

OCH3

CH3

C7H9NO2

3X139.15=417.45

+ POCl3

Phosphorous oxychloride

153.33

MDC

N

Cl

OCH3

CH3

C7H8ClNO

3X157.60=472.8

+ H3PO4

Phosphoric Acid

98.0

3 3

3-Methoxy-2-methyl-1H-pyridin-4-one

4-Chloro-3-methoxy-2-methyl-pyridine



Stage-4:

N

Cl

OCH3

CH3

C7H8ClNO

157.60

+ H2O2

Hydrogen peroxide

34.01

MeOH

Acetic acidN

Cl

OCH3

CH3

O

3-methoxy-2-methyl-4-chloro pyridine-N-oxide

C7H8ClNO

173.60

+ H2O

18.04-Chloro-3-methoxy-2-methyl-pyridine

Stage-5:

N

Cl

OCH3

CH3

O

C7H8ClNO

173.60

+ CH3ONaMeOH

54.02

N

OCH3

OCH3

CH3

O

C8H11NO3169.18

+ NaCl

58.53,4-Dimethoxy-2-methyl

pyridine-N-oxide3,4-Dimethoxy-2-methyl

pyridine-N-oxide

Stage-6:

N

OCH3

OCH3

CH3

O

C8H11NO3

169.18

+ (CH3CO)2O

Acetic anhydride

102.09

MDC

N

OCH3

OCH3

CH2OCOCH3

C10H13NO4

211.21

+ CH3COOH

Acetic acid

60.0Acetic acid 3,4-dimethoxy-

pyridin-2-ylmethyl ester3,4-Dimethoxy-2-methyl pyridine-N-oxide



Stage-7

N

OCH3

OCH3

CH2OCOCH3

C10H13NO4

211.21

+ NaOHMDC

N

OCH3

OCH3

CH2OH

C8H11NO3

169.18

+ CH3COONa

Sodium acetate

82.0340.0Acetic acid 3,4-dimethoxy-

pyridin-2-ylmethyl ester

(3,4-Dimethoxy-pyridin-2-yl)-methanol

Stage-8:

N

OCH3

OCH3

CH2OH

C8H11NO3

169.18

+ SOCl2

Thionyl chloride

118.97

MDC,MeOH

N

OCH3

OCH3

CH2Cl

HCl

224.12

+ SO2

Sulphur dioxide

64.02-Chloromethyl-3,4-dimethoxy-

pyridine Hydrochloride

C8H11Cl2NO2

(3,4-Dimethoxy-pyridin-2-yl)-methanol



Stage-9:

N

OCH3

OCH3

CH2ClHCl

C8H10ClNO2.HCl

224.12

+

NHN

OF

F

SH

5-Difluoromethoxy-2-mercaptobenzimidazole

C8H6F2N2OS

216.21

+ MDC

N

OCH3

OCH3

CH2 SN

HN

OF

F

C16H15F2N3O3S

367.37

+ 2 NH4Cl + 2 H2O

Ammonium chloride

106.98

2x18.0=365-Difluoromethoxy-2-(3,4-dimethoxy-pyridin-2-ylmethylsulfanyl)-

1H-benzoimidazole

2-Chloromethyl-3,4-dimethoxy-pyridine Hydrochloride

Ammonium hydroxide

2 NH4OH

2X35.04=70.08



Stage-10:

N

OCH3

OCH3

CH2 SN

HN

OF

F

C16H15F2N3O3S

367.37

+ NaOCl + NaOHMDC

Acetone

N

OCH3

OCH3

CH2 SN

N

OF

F

O

+ NaCl +Na

H2O

Pantoprazole sodium

C16H14F2N3NaO4S

405.35

Sodium chloride

58.5

18.0

Sodium hypochlorite

74.44

Sodium hydroxide

40.0

5-Difluoromethoxy-2-(3,4-dimethoxy-pyridin-2-ylmethylsulfanyl)-

1H-benzoimidazole



PANTOPRAZOLE SODIUM

Flow Chart:

Stage-1

Stage-2

Stage-3

Stage-4

Stage-5

Stage-6

MaltolDimethyl sulphatePotassium carbonate

Potassium sulfate

Stage-1Ammonium CarbonateToluene

Toluene Rec

Stage-2Phosphorous oxy chlorideMDC

MDC Rec

Stage-3Hydrogen peroxide Acetic acidMethanol

Methanol Rec

Stage-4MethanolSodium methoxide

Methanol Rec

Stage-5Acetic AnhydrideChloroform

Chloroform rec



Stage-7Thionyl chloridechloroform Stage-8 Chloroform Rec

Stage-85-diFluoromethoxy-2-mercapto-benzimidazole

Sodium chlorideStage-9

Stage-9Sodium hypochloriteSodium Hydroxide


PANTOPRAZOLE SODIUM

Stage-6Sodium hydroxideMDC

Stage-7 MDC Rec



PANTOPRAZOLE SODIUM

Material Balance:

Material Balance of Pantoprazole Sodium Stage-1

Batch Size: 200 Kg Name of the input Quantity

in Kg Name of the output Quantity

in Kg Maltol 66.00 Stage-1 73.00 Dimethyl sulphate 33.00 Acetone Recovery 378.00 Potassium carbonate 36.00 Acetone Loss 20.00 Acetone 400.00 Generated water 4.70 Process Emission 11.46 (Carbon dioxide) By-Product 45.60 (Potassium Sulphate) Organic Residue 2.24 (Organic Impurities-0.24,

Acetone-2)





in Kg Stage-1 73.00 Stage-2 72.00 Ammonium Carbonate 50.00 Toluene Recovery 280.00 Toluene 300.00 Toluene Loss 15.00 Water 600.00 Effluent Water 629.57 (Water-600,Ammonium

hydroxide-18.2 ,Generated water-9.37,Toluene-2)

0

Organic Residue 3.53 (Organic Impurities-0.53,

Toluene-3) 0

Process Emission 22.90 (Carbon dioxide) Total 1023.00 Total 1023.00






in Kg Stage-2 72.00 Stage-3 79.00 Phosphorous oxy chloride 26.00 MDC Recovery 285.00 Ammonia 9.00 MDC Loss 15.00 Methylenedichloride 300.00 Effluent Water 600.00 Water 600.00 (Water-600) 0 By-Product 26.30 (Ammonium phosphate) 0 Organic Residue 1.70 Total 1007.00 Total 1007.00




in Kg Stage-3 79.00 Stage-4 87.00 Hydrogen peroxide 17.00 MDC Recovery 668.00 Acetic acid 30.00 MDC Loss 30.00 Methanol 250.00 Methanol Recovery 233.00 Sodium Hydroxide 20.00 Methanol Loss 12.50 MDC 700.00 Effluent Water 419.50 Water 400.00 (Water-400, Generated

water-17, Methanol-2.5)

By-Product 41.00 (Sodium acetate) Organic Solid Waste 5.00 (Organic Impurities-

1,MDC-2,Methanol-2)

Total 1496.00 Total 1496.00




Batch Size: 200 Kg Name of the input Quantity


in Kg Stage-4 87.00 Stage-5 85.00 Methanol 500.00 Methanol Recovery 465.00 Sodium methoxide 27.00 Methanol Loss 20.00 Acetic Acid 10.00 Effluent Water 642.20 Water 600.00 (Water-600, Sodium

Chloride-29.2,Methanol-3,Acetic acid-10)

0





in Kg Stage-5 85.00 Stage-6 106.00 Acetic Anhydride 172.00 Chloroform Recovery 190.00 Chloroform 200.00 Chloroform Loss 10.00 Water 400.00 Acetic acid Recovery 101.00 Effluent Water 400.00 (Water-400) 0 Organic Residue 50.00 Total 857.00 Total 857.00






in Kg Stage-6 106.00 Stage-7 85.00 MDC 200.00 MDC Recovery 190.00 Sodium hydroxide 20.00 MDC Loss 10.00 Water 200.00 Effluent Water 200.00 (Water-200) By-Product 41.00 (Sodium acetate) Total 526.00 Total 526.00




in Kg Stage-7 85.00 Stage-8 (Chloro

compound) 112.00

Thionyl chloride 60.00 Chloroform Recovery 810.00 Chloroform 850.00 Chloroform Loss 40.00 Methanol 125.00 Methanol Recovery 99.00 Acetone 200.00 Methanol Loss 25.00 Acetone Recovery 189.00 Acetone Loss 10.00 Process Emission 32.00 (Sulphur Dioxide) Organic Residue 3.00 (Organic Impurities-1,

Methanol-1,Acetone-1)

Total 1320.00 Total 1320.00






in Kg Stage-8 112.00 Stage-9 183.00 5-diFluoromethoxy-2-mercaptobenzimidazole

108.00 Toluene Recovery 472.00

Ammonium hydroxide 35.50 Toluene Loss 25.00 Toluene 500.00 Effluent Water 619.50 Water 600.00 (Water-600, gen.Water-

18, Toluene-1.5) 0

B-Product 54.19 (Ammonium chloride) 0 Organic Residue 1.81 (Organic Impurities-0.31,

Toluene-1.5)

Total 1355.50 Total 1355.50

Material Balance of Pantoprazole Sodium Stage-10:Pharma Batch Size: 200Kg

Name of the input Quantity in Kg

Name of the output Quantity in Kg

Stage-8 183.00 Pantoprazole Sodium 200.00 Sodium hypochlorite 37.00 MDC Recovery 950.00 Sodium Hydroxide flakes 20.00 MDC Loss 50.00 Ammonium Chloride 25.00 Acetone Recovery 378.00 Methylene dichloride 1000.00 Acetone Loss 20.00 Activated Carbon 10.00 Effluent Water 465.00 Acetone 400.00 (Water-400,gen.water-9,

Sodium chloride-29, Aluminum chloride-25, Acetone-2)

0

Water 400.00 Spent carbon 10.00 Organic Residue 2.00 Total 2075.00 Total 2075.00



15. PHENYL MAGNESIUM CHLORIDE

Process Description

Stage-1



temperature. Start and continue the addition of Chlorobenzene up to completion of

the reaction. Maintain for few hours and cool to room temperature. Check Product

and unload the material into the containers under nitrogen atmosphere.

PHENYL MAGNESIUM CHLORIDE

Route of Synthesis:

Stage-1:

Mg +

Magnesium

24.31

Chlorobenzene

Cl

C6H5Cl

112.56

MgCl

C6H5ClMg

Phenyl Magnesium chloride

136.86

THF




Flow Chart:

Stage-1


THF RecoveryChlorobenzeneMagnesium turningsTHF


Material Balance:

Material Balance of phenyl Magnesium Chloride Stage-1



in Kg

Chlorobenzene 820.00 Phenyl Magnesium Chloride in THF Solution

1750.00

Magnesium turnings 180.00 THF Loss 50.00 THF 800.00 Total 1800.00 Total 1800.00



16. QUETIAPINE FUMARATE


Stage-1

2-Aminbiphenylsulphate when reacts with Phenyl chloro fumarate, the compound is

formed. Toluene is the solvent .Toluene layer is washed with water to remove acidic

salts that form during the reaction.

Stage-2

Stage-1 compound is hydrolyzed in presence of Phosphoric acid to obtain the stage-

2 compound. Acetone wash is given to remove water traces.

Stage-3

Stage-2 compound made to react with Piperazine in Toluene medium to produce the

stage -3 compound.

Stage-4

Stage-3 is converted to pharma by treating with Chloro ethoxy ethanol and Fumaric

acid in Toluene medium. Toluene layer is washed with water to remove water

soluble impurities. Finally the pharma is re-crystallized in Methanol.



QUETIAPINE FUMARATE

Route of synthesis:

Stage-1:

O

NH2

S OOO

2-Aminodiphenyl sulphate

C12H11NO4S

265.29

+

-O O

Cl

O-O

Phenyl chloro fumarate

C10H5ClO4

224.60

Toluene

S

NH O

O

Phenyl-2-(phenyl carbamate

C19H15NO2S

321.39

+

Hydroperoxy-hydroxy-acetyl chloride

+ CO2

Carbondioxide

44.01C2HClO4

124.48

O

HO OOH

Cl



Stage-2:

S

NH O

O

Phenyl-2-(phenyl carbamate

C19H15NO2S

321.39

S

HN

OH

Dibenzo,1,4-thiozepin,1-H-one

C13H11NOS

229.30

+Phosphoric acid

Hydrogen

H2

2.00

+

Phenol

OH

94.11

C6H6O

Stage-3:

S

HN

OH

Dibenzo,1,4-thiozepin 1-H-one

C13H11NOS

229.30

+ HN NH

Piperazine

C4H10N2

86.14

Toluene

S

HN

N

+ H2O

18.00

NH

11-Piperazin-1-yl-5a,9a,10,11-tetrahydro-dibenzo[b,f]

[1,4]thiazepineC17H19N3S

297.42



Stage-4:

Step-A

S

HN

N

NH

11-Piperazin-1-yl-5a,9a,10,11-tetrahydro-dibenzo[b,f]

[1,4]thiazepineC17H19N3S

297.42

+ HOO

Cl

2-(2-Chloro-ethoxy)-ethanol

C4H9ClO2

124.57

Toluene

S

HN

N

NO

Cl

11-{4-[2-(2-Chloro-ethoxy)-ethyl]-piperazin-1-yl}-10,11-dihydro-dibenzo[b,f]

[1,4]thiazepineC21H26ClN3OS

403.97

+ H2O

18.00



Step-B

S

HN

N

NO

Cl

11-{4-[2-(2-Chloro-ethoxy)-ethyl]-piperazin-1-yl}-10,11-dihydro-dibenzo[b,f]

[1,4]thiazepineC21H26ClN3OS

403.97

+

Fumaric acid

O OH

OHO

C4H4O4

116.07

S

HN

N

NO

OHO Cl

OHO

+

QuetiapineC21H27N3O2S

385.52

Chloro fumaric acid

Toluene

C4H3ClO3

134.52



Step-C

+

Fumaric acid

O OH

OHO

C4H4O4

116.07

S

HN

N

NO

OH

Quetiapine

2X385.52=770.00

2

S

HN

N

NO

OH

2

O OH

OHO

Quetiapine fumarate

C42H50N6O4S2

C46H54N6O8S2

886.07



QUETIAPINE FUMARATE

Flow Chart:

2-AminbiphenylsulphatePhenyl chloro fumarateToluene

Toluene RecStage-1

Stage-2Stage-1phosphoric acidAcetone

Acetone Rec

Stage-3Stage-2PiperazineToluene

Toluene Rec

Stage-4Stage-3Chloro ethoxy ethanolFumaric acidMethanol.

Methanol Rec

QUETIAPINE FUMARATE



QUETIAPINE FUMARATE

Material Balance:

Material Balance of Quetiapine fumarate Stage-1



in Kg 2-Aminbiphenylsulphate 140.00 Stage-1 165.00 Phenyl chloro fumarate 118.50 Toluene Recovery 378.00 Toluene 400.00 Toluene Loss 20.00 Water 200.00 Effluent Water 266.60 (Water-200,Chloro-oxo

ethane peroxic acid-65.6, Toluene-1)

Process Emission 23.21 (Carbon dioxide) Organic Residue 5.69 (Organic Impurities-4.69,

Toluene-1)





in Kg Stage-1 165.00 Stage-2 115.00 phosphoric acid 46.70 Acetone Recovery 372.00 Acetone 400.00 Acetone Loss 20.00 Hydrogen gas 1.02 Effluent Water 324.80 Water 250.00 (Water-250,Acetic Acid-

20.1,Acetone-8,Phosphoric Acid-46.7)

Phenol Recovery 30.92 Total 862.72 Total 862.72






in Kg Stage-2 115.00 Stage-3 140.00 Piperazine 44.00 Toluene Recovery 332.00 Toluene 350.00 Toluene Loss 17.00 Gen. Water 9.02 Organic Residue 10.98 (Organic Impurities-9.98,

Toluene-1)


Material Balance of Quetiapine fumarate Stage-4 Pharma



in Kg Stage-3 140.00 Quetiapine fumarate 200.00 Chloro ethoxy ethanol 59.00 Toluene Recovery 380.00 Fumaric acid 85.00 Toluene Loss 20.00 Methanol. 400.00 Methanol Recovery 377.00 Toluene 400.00 Methanol Loss 20.00 Water 800.00 Effluent Water 873.76 (Water-800,gen.water-8.46,

Methanol-2, Chloro fumaric acid-63.3)

Organic Residue 13.24 (Organic Impurities-12.24,

Methanol-1)

Total 1884.00 Total 1884.00



17. RABEPRAZOLE SODIUM

Process Description

Stage-1

2, 3-Lutidine is reacted with Hydrogen Peroxide in presence of Acetic Acid to give N-Oxide it further reacts with Nitration mixture (Nitric Acid + Sulfuric Acid) to give Stage-1

Stage-2

Stage-1 is reacted with 3-Methoxy-1-Propanol and Sodium Hydroxide to get Stage-2 Compound

Stage-3

Stage-2 Compound is reacted with Acetic Anhydride, Sodium Hydroxide and Hydrochloric Acid to get Stage-3 Compound

Stage-4

Stage-3 Compound is reacted with Thionyl Chloride, 2Mercapto benzimidazole and sodium hydroxide in the presence of MDC as a solvent media to give stage-4 as product.

Stage-5

Stage-4 Compound is reacted with Sodium Hypochlorite to get Rabeprazole Base

Stage-6

Stage-5 reacts with Sodium hydroxide to get Rabeprazole Sodium



RABEPRAZOLE SODIUM

Route of Synthesis:

Stage-1:

N

CH3

CH3

2,3-Lutidine

C7H9N

107.15

+ H2O2

Hydrogen peroxide

34.01

+ HNO3

Niric acid

63.0

H2SO4

N

CH3

CH3

+

O

NO2

C7H8N2O3

168.15

2H2O

36.04-Nitro-2,3-Dimethyl

pyridine-N-oxide

Stage-2:

N

CH3

CH3O

NO2

C7H8N2O3

168.15

4-Nitro-2,3-Dimethyl pyridine-N-oxide

3-Methoxy-1-Propanol

HO O

4(3-Methoxy propoxy)-2,3-Dimethyl pyridine-N-oxide

N+

O-

H3C

H3C

O O

+ NaOH+

C4H10O2

90.12 C11H17NO3

211.26

+ NaNO2 + H2O

Sodium Nitrite

69.0

18.0

40.0



Stage-3:

4(3-Methoxy propoxy)-2,3-Dimethyl pyridine-N-oxide

N+

O-

H3C

H3C

O O

C11H17NO3

211.26

+(CH3CO)2O + NaOH

4(3-methoxy propoxy)-2-hydroxy methyl -3-methyl pyridine

hydrochloride

N

O O

HO + CH3COONa + CH3COOH

82.0 60.0

Acetic Anhydride

102.0

40.0

C11H17NO3 HCl

HCl

247.72

+ HCl

36.5

Stage-4:

4(3-methoxy propoxy)-2-hydroxy methyl -3-methyl pyridine

hydrochloride

N

O O

HO

C11H17NO3 HCl

HCl

247.72

+ SOCl2N

O O

Cl

4-(3-methoxy-propoxy)-2-Chloromethyl-3-methyl-

Pyridine

ThionylChloride

118.97 C11H16ClNO2

229.7

+ SO2

+ 2 HCl

64.0

2X36.5=73



Stage-5:

N

O O

Cl

4-(3-methoxy-propoxy)-2-Chloromethyl-3-methyl-

pyridineC11H16ClNO2

229.7

2-Mercapto benzimidazole

N

HN

HS+ +

35.05

NCH2

O O

N

NH

S

2-[4-(3-Methoxy-propoxy)-3-methyl-pyridin-2-ylmethylsulfanyl]-1H-benzoimidazole

NH4OH

C18H21N3O2S

343.44

+ NH4Cl + H2O

53.49 18.0

C7H6N2S150.25



Stage-6:

NCH2

O O

N

NH

S

2-[4-(3-Methoxy-propoxy)-3-methyl-pyridin-2-ylmethylsulfanyl]-


343.44

+NaOCl NC

H2

O O

N

NH

S

O

SodiumHypochlorite

2-[4-(3-Methoxy-propoxy)-3-methyl-pyridin-2-ylmethanesulfinyl]-


359.44

+ NaCl

58.5

74.44

Stage-7:

NCH2

O O

N

NH

S

O

2-[4-(3-Methoxy-propoxy)-3-methyl-pyridin-2-ylmethanesulfinyl]-


359.44

+ NaOH NCH

O O

N

NH

S

O

Na

Rabeprazole Sodium40.0

+ H2O

18.0C18H20N3NaO3S

381.42



RABEPRAZOLE SODIUM Flow Chart:

2,3 LutidineHydrogen peroxideNitric acid

Generated waterStage-1

Stage-13-Methoxy-1-propanolSodium hydroxide

Sodium nitriteStage-2

Stage-23-Methoxy-1-propanolAcetic anhydride

Stage-3 Sodium acetate

Stage-3Thionyl chloride

Sulphur dioxideStage-4

Stage-42-mercaptobenzimidazole

Stage-5 Sodium chloride

Stage-5Sodium hypochlorite


RABEPRAZOLE SODIUM

Stage-7Stage-6Sodium hydroxide

Generated water



RABEPRAZOLE SODIUM

Material Balance:

Material balance of Rabeprazole Sodium Stage-1



in Kg 2,3-Lutidine 46.00 Stage-1 65.00 Hydrogen Peroxide (50%) 33.00 Effluent Water 350.80 Nitric acid 38.00 (Water-300 ,Acetic Acid-

6,Hydrogen Peroxide-1.9,Nitric Acid-10.9, gen. water-15.5,Water from Hydrogen peroxide-16.5)

0

Acetic acid 6.00 Organic Residue 7.20 Water 300.00 Total 423.00 Total 423.00




in Kg Stage-1 65.00 Stage-2 80.00 3-Methoxy-1-Propanol 43.00 Toluene Recovery 235.00 Sodium Hydroxide 15.50 Toluene Loss 12.00 Toluene 250.00 DMSO Recovery 188.00 DMSO 200.00 DMSO Loss 10.00 Generated water 7.00 By-Product 29.70 (Sodium Nitrite-29.7) Organic Solid Waste 11.80

(Organic Impurities-6.8,

Toluene-3,DMSO-2)







in Kg Stage-2 80.00 Stage-3 90.00 Acetic anhydride 39.00 Toluene Recovery 660.00 Sodium Hydroxide 15.00 Toluene Loss 35.00 Hydrochloric acid 20.00 Effluent Water 302.00 Toluene 700.00 (Water-300, Toluene-2) Water 300.00 Acetic Acid Recovery 25.20 By-Product 34.50 (Sodium Acetate) Organic Residue 7.30 (Organic Impurities-

4.3,Toluene-3)

Total 1154.00 Total 1154.00




in Kg Stage-3 90.00 Stage-4 80.00 Thionyl Chloride 53.00 MDC Recovery 710.00 MDC 750.00 MDC Loss 37.00 Sodium Sulphate 10.00 Effluent Water 426.50 Water 400.00 (Water-400,Hydrochloric

acid-26.5)

Inorganic Solid Waste 10.00 (Sodium Sulphate) Organic Residue 16.30 (Organic Impurites-13.3,

MDC-3)

Process Emission 23.20 (sulfur dioxide) Total 1303.00 Total 1303.00






in Kg Stage-4 80.00 Stage-5 100.00 2-Mercaptobenzimidazole 53.00 Toluene Recovery 375.00 Ammonium hydroxide 12.50 Toluene Loss 20.00 Toluene 400.00 Effluent Water 308.42 Water 300.00 (Water-300, generated

water-6.42,Toluene-2)

By-Product 19.07 (Ammonium chloride) Organic Residue 23.01 (Organic Impurites-

20.01, Toluene-3)





in Kg Stage-5 100.00 Stage-6 100.00 Sodium Hypochlorite (8%) 327.00 MDC Recovery 570.00 MDC 600.00 MDC Loss 30.00 Acetone 150.00 Acetone Recovery 137.00 Sodium hydro sulphate 12.00 Acetone Loss 10.00 MMA in Methanol 10.00 Effluent Water 1344.30 Water 1000.00 (Water-1000,Sodium

Chloride-17,water from sodium hypochlorite-300,Sodium Hypochlorite-5.3,MMA-10, Sodium hydrosulphate-12)

0

Organic Solid Waste 7.70 (Organic Impurities-4.7,

Acetone-3) 0

Total 2199.00 Total 2199.00



Material balance of Rabeprazole Sodium Stage-7:Pharma



in Kg Stage-6 100.00 Rabeprazole Sodium 100.00 Sodium Hydroxide 13.00 IPA Recovery 280.00 Isopropyl Alcohol 300.00 IPA Loss 15.00 Activated Carbon 10.00 Generated water 5.00 Spent carbon 10.00 Organic Residue 13.00 (Organic Impurities-

8,IPA-5)




18. SODIUM METHOXIDE

Process Description

Stage-1

Sodium hydroxide reacts with Methanol to give sodium methoxide,by eliminating

water.

SODIUM METHOXIDE

Route of Synthesis

Stage-1

NaOH

Sodium hydroxide

40.00

+ CH3OH

Methanol

32.04

CH3ONa

54.02

Sodium methoxide

+ H2O

18.02

SODIUM METHOXIDE

Flow Chart

Stage-1

SODIUM METHOXIDE

Methanol RecSodium hydroxideMethanol



SODIUM METHOXIDE

Material Balance:

Material Balance of Sodium methoxide Stage-1



in Kg Sodium hydroxide 1482.00 Sodium methoxide in Methanol 2000.00 Methanol 1700.00 Methanol Recovery 475.00 Methanol Loss 38.00 Generated water 668.00 Organic Residue 1.00 Total 3182.00 Total 3182.00



19. SODIUM TERT BUTOXIDE

Process Description

Stage-1

Sodium is added into excess tert-butanol in a rotary drier cum reactor. Excess Tert-

Butanol is used to ensure the complete reaction of the corresponding metals. Then

the excess Tert-Butanol is recovered by thermic fluid heating through a condensor

and used again in the next batches. A small quantity of hydrogen is let out through a

liquid paraffin trap.

SODIUM TERT BUTOXIDE

Route of Synthesis

Stage-1:

Na

22.99

+

Tert-Butanol

CH3

H3C

CH3

OH

CH3

H3C

CH3

ONa

Sodium metalC4H10O

74.12

Sodium tert-butoxide

96.10

+ 1/2 H2

Hydrogen gas

1/2X2=1.00C4H9ONa




Flow Chart:

Stage-1SodiummetalTert-Butanol

Hydrogen gasTert-Butanol Rec

SODIUM TERT- BUTOXIDE


Material Balance:

Material Balance of Sodium tert-Butoxide Stage-1

Batch Size:500.0 Kgs Name of the input Quantity


in Kg Sodium 141.18 Sodium tert-Butoxide 500.00 Tert-Butanol 650.00 t-Butanol Recovery 271.25 t-Butanol Loss 15.48 Process Emission 4.45 (Hydrogen-4.45) Total 791.18 Total 791.18



20. TELMISARTAN

Process Description Stage-1 Step-A Methyl-4-(butyramido)3-methyl-5-nitrobenzoate undergoes hydrogenation in the presence of Palladium carbon as catalyst by using Methanol as solvent media to give Stage-1A as product. Step-B Stage-1A product reacts with sodium hydroxide and hydrochloric acid to give Stage-1B as product. Stage-2 Stage-1 B product reacts with N-Methylbenzene-1,2-diamine in the presence of Sodium hydroxide and polyphosphoric acid to give Stage -2 as product. Stage-3 Stage-2 product reacts with 1, 3-dibromo-5, 5-dimethylimidazolidine-2,4-dione in the presence of Chloroform as solvent media to give Stage-3 as product. Stage-4 Stage-2 product reacts with Stage-3 and potassium hydroxide in the presence of acetone as solvent media to give Stage-4 as product. Stage-5 Stage-4 product reacts with potassium hydroxide and hydrochloric acid in the presence of MDC as solvent media to give stage-5 as product. Stage-6 Stage-5 product undergoes purification with Methanolic ammonia, acetic acid and activated carbon in the presence of methanol as solvent media to give Telmisartan as product.



TELMISARTAN

Route of Synthesis:

Stage-1

Step-A

methyl-4-(buytramido)-3-methyl-5-nitrobenzoate

H3CO

O

NO2

NH

O + H2

Hydrogen

C13H16N2O5

280.28

2.0

H3CO

O

NH2

NH

OPd/C

MeOH

Methyl-3-amino-4-(buytramido)-5-methylbenzoate

C13H18N2O3

250.29

+ O2

Oxygen

32.0

Step-B

H3CO

O

NH2

NH

O

Methyl-3-amino-4-(buytramido)-5-methylbenzoate

C13H18N2O3250.29

+ NaOH + HCl

Sodium hydroxide

40.0

Hydrochloric acid

36.5

7-Methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid

NH

N

O

OH

C12H14N2O2

218.25

+ CH3OH

Methanol

32.0

+ NaCl

Sodium chloride

58.5

+ H2O

Water18.0



Stage-2

7-Methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid

NH

N

O

OH

C12H14N2O2

218.25

N-Methylbenzene-1,2-diamine

NH

NH2

+

C7H10N2

122.17

4-Methyl-6-(1-methyl-1H-benzoimidazol-2-yl)-2-propyl-1H-benzo imidazole

N

NH

N

NNaOH

PPA

C19H20N4

304.39+ 2H2O

36.0

H3PO4 + 3 NaOH Na3PO4 + 3 H2O

Phosphoric Acid Sodium hydroxide Sodium phosphate Water

98.0 3X40=120 163.94 3X18=54

Stage-3

methyl-4-methyl-1,1-biphenyl-2-carboxylate

H3C

COOCH3

C15H14O2

226.27

+

1,3-Dibromo-5,5-dimethylimidazolidine-2,4-dione

NN

O

O

Br

Br

C5H6N2O2

285.92

BrH2C

COOCH3

Chloroform

4-(bromomethyl)biphenyl-2-carboxylic acid methyl ester

C15H13BrO2

305.17

+

1-Bromo-5,5-dimethylimidazolidine-2,4-dione

HNN

O

O

Br

C5H7BrN2O2

207.03



Stage-4

4-Methyl-6-(1-methyl-1H-benzoimidazol-2-yl)-2-propyl-1H-benzo imidazole

N

NH

N

N

C19H20N4

304.39

BrH2CCOOCH3

4-(bromomethyl)biphenyl-2-carboxylic acid methyl ester

C15H13BrO2

305.17

++ KOH

Potassium hydroxide

56.11

Acetone

methyl-4-[[2n-propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)-benzimidazole-1-yl]-methyl]biphenyl carboxylate

N

N

N

N

COOCH3

C34H32N4O2

528.64

+ KBr

119.0

+ H2O

18.0



Stage-5

methyl-4-[[2n-propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)-benzimidazole-1-yl]-methyl]biphenyl carboxylate

N

N

N

N

COOCH3

C34H32N4O2

528.64

+ KOH

Potassium hydroxide

56.11

+ HCl

Hydrochloric acid

36.5

N

N

N

N

COOH

MeOH

4-[[2n-Propyl-4-methyl-6-(1-methyl benzimidazole-2-yl)-benzimidazole-1-yl]-methylbiphenyl carboxylic acid

C33H30N4O2

514.62

+ CH3OH + KCl

32.0 74.55



Stage-6

N

N

N

N

COOH

4-[[2n-Propyl-4-methyl-6-(1-methyl benzimidazole-2-yl)-benzimidazole-1-yl]-methylbiphenyl carboxylic acid

C33H30N4O2

514.62

+ CH3OH NH3

Methanolic ammonia

CH7NO

49.07

+ CH3COOH

Acetic acid

60.0

MeOH

N

N

N

N

COOH

+

Telmisaratn

C33H30N4O2

514.62

+ CH3OH

Ammonium acetate

CH3COONH4

77.08

Methanol

32.0



TELMISARTAN

Flow chart:

Stage-155.0 Kg

ProductMethanol Rec

Effluent water

Stage-273.0 Kg

Product

Effluent water

Stage-373.50 Kg

Productn-Hexane Rec

Effluent water

Stage-1N-Methylbenzene-1,2-diaminePoly phosphoric acidSodium hydroxide

Stage-4123.0 Kg

ProductAcetone Rec

Effluent water

Stage-5115.0 Kg

ProductCarbon Dioxide

Effluent water

Stage-6100.0 Kg

ProductMethanol Rec

Effluent water

TELMISARTAN

Methyl-4-(butyramido)-3-methyl-5-nitrobenzeneMethanolPalladium carbon(Wet 5% MC)Sodium hydroxideHydrochloric acid

Methyl-4-methyl-1,1-biphenyl-2-carboxylate1,3-dibromo-5,5-dimethyl imidazolidine-2,4-dioneSodium meta bisulphateChloroformn-Hexane

Stage-4Potassium hydroxideMDCMethanolHydrochloric acid (20%)

Stage-2Stage-3Potassium hydroxideAcetone

Stage-5Methanolic ammoniaAcetic acidMethanol



TELMISARTAN

Material Balance:

Material Balance of Telmisartan Stage-1



in Kg Methyl-4-(butyramido)-3-methyl-5-nitrobenzene

73.00 Stage-1 55.00

Methanol 865.00 Methanol Recovery 822.00 Palladium carbon(Wet 5% MC) 3.00 Methanol Loss 43.00 Sodium hydroxide 10.40 Effluent water 550.20 Hydrochloric acid 31.60 (Water-500,generated water-4.6,

Sodium chloride-15.2,Hydrochloric acid-22.1, Methanol-8.3)

Water 500.00 Palladium Carbon Reuse 3.00 Process Emission 8.33 (Oxygen) Organic Residue 1.47 Total 1483.00 Total 1483.00




in Kg Stage-1 55.00 Stage-2 73.00 N-Methylbenzene-1,2-diamine 32.00 Effluent Water 658.67 Phosphoric acid 90.00 (Water-600,generated water-58.67) Sodium hydroxide 110.20 By-Product 150.56 Water 600.00 (Sodium Phosphate) Organic Residue 4.97 Total 887.20 Total 887.20






in Kg Methyl-4-methyl-1,1-biphenyl-2-carboxylate

57.00 Stage-3 73.50

1,3-dibromo-5,5-dimethyl imidazolidine-2,4-dione

72.00 Chloroform Recovery 304.00

Azo bis isobutyronitrile 2.90 Chloroform Loss 16.00 Sodium meta bisulphate 4.30 n-Hexane Recovery 95.00 Chloroform 320.00 n-Hexane Loss 5.00 n-Hexane 100.00 Effluent water 407.20 Water 400.00 (Water-400,Sodium meta

bisulphate-4.3,Azobis isobutyronitrile-2.9,)

By-Product 52.13 (1-Bromo-5,5-dimethyl imidazoline-

2,4-dione)

Organic Solid Waste 3.37 Total 956.20 Total 956.20

Material Balance of Telmisartan Stage-4 Batch Size: 100Kg Name of the input Quantity


in Kg Stage-2 73.00 Stage-4 123.00 Stage-3 73.50 Acetone Recovery 427.00 Potassium hydroxide 18.00 Acetone Loss 22.00 Acetone 450.00 Effluent water 939.30 Water 900.00 (Water-900,generated water-4.3,

Potassium hydroxide-4.5,Acetone-2,Potassium bromide-28.5)

Organic Residue 3.20 (Organic Impurities-2.2,Acetone-1) Total 1514.50 Total 1514.50






in Kg Stage-4 123.00 Stage-5 115.00 Potassium hydroxide 15.00 MDC Recovery 1138.00 MDC 1200.00 MDC Loss 60.00 Methanol 1000.00 Methanol Recovery 948.00 Hydrochloric acid (20%) 50.00 Methanol Loss 50.00 Acetic acid 40.00 Effluent water 706.20 Activated carbon 5.00 (Water-600,Potassium chloride-

17.3,Methanol-7.4,Acetic acid-40, water from HCl-40,Hydrochloric acid-1.5)

Water 600.00 Spent Carbon 5.00 Organic Residue 10.80 (Organic Impurities-6.8, Methanol-

2,MDC-2)

Total 3033.00 Total 3033.00




in Kg Stage-5 115.00 Telmisartan 100.00 Methanolic ammonia 50.00 Methanol Recovery 833.00 Acetic acid 20.00 Methanol Loss 40.00 Methanol 830.00 Effluent water 234.40 Activated carbon 5.00 (Water-230,Acetic acid-2.4,

Methanol-2)

By-Product (Ammonium acetate) 22.70 Water 230.00 Spent Carbon 5.00 Organic Residue 7.90 Total 1243.00 Total 1243.00



Annexure - III

WATER CONSUMPTION DETAILS

S. No Purpose Water

Requirement In KLD

1 Process 49.82 2 Washings 2.00 3 Boiler Make up 58.50 4 Cooling towers Make up 144.50 5 DM Plant 2.00 6 Scrubbing system 2.00 7 Domestic usage 2.00 8 Gardening 5.00

Total 266.0



Annexure - IV

HAZARDOUS WASTE DETAILS

S. No Name of the Hazardous Waste

Quantity Kg/Day Disposal Method

1 Organic waste 1254.00 Sent to Cement Industries 2 Spent Carbon 146.00 Sent to Cement Industries 3 Solvent Distillation Residue 176.00 Sent to Cement Industries 4 Inorganic Waste 279.00 Sent to TSDF 5 MEE Salts 5990.0 Sent to TSDF 6 ETP Sludge 50.00 Sent to TSDF 7 Used Oils 800

L/Annum SPCB Authorized Agencies for Reprocessing/Recycling

8 Detoxified Containers 600 No’s /

Month

After Detoxification sent back to suppliers/SPCB Authorized Parties

9 Used Lead Acid Batteries 4 No’s/ Annum

Send back to suppliers for buyback of New Batteries

Solid Waste Details 10 Coal ash from boiler 11750 Sent to Brick Manufacturers



Annexure - V

STACK EMISSIONS FOR PROPOSED BOILERS

Particulars Units 10.0 TPH Coal fired

Boiler (Proposed)

6.0 TPH Coal fired Boiler (Stand By )

Type of Fuel -- Indian Coal Indian Coal Coal Consumption TPD 25.0 15.0 Ash Content % 47 47 Sulphur Content % 0.8 0.8 Nitrogen Content % 1.07 1.07 No. of Stacks No 1 1 Height of stack M 32 30 Diameter of Stack M 0.80 0.60 Temperature of Flue Gas oC 140 110 Velocity of Flue Gas m/s 8.50 8.50 Particulate Matter at outlet of Bag filter (Based on 115 mg/Nm3 at outlet)

gm/sec 0.74 0.62

Sulphur dioxide emission gm/sec 2.31 1.39 Oxides of Nitrogen emission gm/sec 3.01 1.86

Pollution control equipment

-

Cyclone separator followed by suitable pack of Bag filters

Cyclone separator followed by

suitable pack of Bag filters

6 TPH Coal fired boiler is kept as stand by

STACK EMISSION DETAILS FOR EXISTING & PROPOSED 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.

275 KVA (Existing)

67.0 118.0 140.0 0.25 200 10 18.50

500 KVA (Existing) 80.0 190.0 235.0 0.30 220 12 23.20

275KVA (Proposed)

67.0 118.0 140.0 0.25 200 10 18.50



Annexure - VI

EXPECTED PROCESS EMISSION DETAILS

S. No Name of the Gas Quantity

In Kg/Day

Treatment Method

Polluting Process Emission Details 1 Ammonia 95.00 Scrubbed by using chilled water media 2 Sulphur dioxide 248.00 Scrubbed by using C. S. Lye solution

Non- Polluting Process Emission Details 1 Carbon dioxide 150.00 Dispersed into atmosphere 2 Oxygen 8.00 Dispersed into atmosphere

3 Hydrogen 30.00 Diffused by using Nitrogen through Flame arrestor

4 Methane 103.00 Dispersed into atmosphere through Nitrogen



Annexure - VII

LIST OF RAW MATERIALS

1. BENZYL MAGNESIUM CHLORIDE

S. No Raw Material Used /Batch in Kgs

Used/ Day in Kgs Source

1 Magnesium 160.00 53.33 Indigenous 2 Benzyl chloride 840.00 280.00 Indigenous 3 Diethyl ether 770.00 256.67 Indigenous 4 Tetrahydrofuran 1100.00 366.67 Indigenous

2. BUTYL MAGNESIUM CHLORIDE



1 Magnesium Metal 210.00 105.00 Indigenous 2 Butyl Chloride 790.00 395.00 Indigenous 3 THF 805.00 402.00 Indigenous

3. DOMPERIDONE



1 N-Carbethoxy-4-piperidone 80.00 266.67 Indigenous

2 1-(3-Chloropropyl)-1,3-dihydro-2H-benzimedazole-2-one

40.00 133.33 Indigenous

3 2,5-Dichloro Nitrobenzene 78.00 260.00 Indigenous 4 Ammonia gas 28.00 93.33 Indigenous 5 Hydrogen 10.00 33.33 Indigenous 6 Methanol 800.00 2666.67 Indigenous 7 Methyl Isobutyl Ketone 1200.00 4000.00 Indigenous 8 Raney Nickel 30.00 100.00 Indigenous 9 Sodium Carbonate 50.00 166.67 Indigenous

10 Sodium Hydroxide 75.00 250.00 Indigenous 11 Toluene 350.00 1166.67 Indigenous 12 Urea 20.00 66.67 Indigenous



4. ESCITALOPRAM OXALATE



1 Bromo phthalide 110.00 110.00 Indigenous 2 Acetic acid 121.00 121.00 Indigenous 3 Acetone 1724.00 1724.00 Indigenous 4 Activated carbon 80.30 80.30 Indigenous 5 Ammonia Liq 204.00 204.00 Indigenous 6 Caustic flakes 38.30 38.30 Indigenous 7 Copper cyanide 45.00 45.00 Indigenous 8 Copper iodide 57.00 57.00 Indigenous

9 Dimethyl amino propyl magnesium chloride 76.00 76.00 Indigenous

10 DMF 2288.00 2288.00 Indigenous 11 Ethylene di amine 267.00 267.00 Indigenous 12 Fluoro bromo benzene 103.00 103.00 Indigenous 13 Hydro bromic acid 41.00 41.00 Indigenous 14 Hyflow 10.00 10.00 Indigenous 15 Iodine 3.00 3.00 Indigenous 16 IPA 4200.00 4200.00 Indigenous 17 Isopropyl ether 240.00 240.00 Indigenous 18 Magnesium turnings 28.00 28.00 Indigenous 19 Methane sulfonyl chloride 50.00 50.00 Indigenous 20 MPR 173.00 173.00 Indigenous 21 Oxalic acid 74.00 74.00 Indigenous 22 Sodium chloride 20.00 20.00 Indigenous 23 Sodium hydroxide 10.00 10.00 Indigenous 24 Sodium sulfate 260.00 260.00 Indigenous 25 Tetrahydrofuran 1000.00 1000.00 Indigenous 26 Toluene 20950.00 20950.00 Indigenous 27 Triethylamine 15.00 15.00 Indigenous

5. ESOMEPRAZOLE MAGNESIUM TRIHYDRATE



1 Omeprazole sulfide 88.00 146.67 Indigenous 2 Cumin hydro peroxide 41.00 68.33 Indigenous 3 Potassium hydroxide 15.20 25.33 Indigenous 4 DET 11.30 18.83 Indigenous 5 Titanium isopropoxide 2.50 4.17 Indigenous 6 NEDIPA 4.50 7.50 Indigenous 8 Toluene 320.00 533.33 Indigenous 9 Methanol 100.00 166.67 Indigenous 10 Magnesium sulfate 16.00 26.67 Indigenous



6. ETHYL MAGNESIUM CHLORIDE



1 Ethyl Chloride 724.00 362.00 Indigenous 2 Mg turnings 276.00 138.00 Indigenous 3 THF 1500.00 750.00 Indigenous

7. LINEZOLID



1 N-[3-Phthalimido-2R-hydroxypropyl-3-fluoro-4-morpholinyl aniline


2 Carbonyl di imidazole 43.25 32.03 Indigenous 3 Hydrazine Hydrate 13.35 9.89 Indigenous 4 Acetic anhydride 27.23 20.17 Indigenous 5 Methanol 753.00 557.72 Indigenous 6 MDC 2682.00 1986.47 Indigenous 7 Activated carbon 10.80 8.00 Indigenous 8 Ethyl acetate 805.00 596.24 Indigenous 9 Acetone 1548.00 1146.55 Indigenous

8. LOPERAMIDE HYDROCHLORIDE



1 N-[(2Z)-3-(diphenylmethyl)dihydrafuran-2(3H)-ylidene]methanamine


2 4-(Chloro phenyl)-Piperidine-4-ol 75.00 27.78 Indigenous

3 Potassium carbonate 25.00 9.26 Indigenous 4 Potassium Iodide 1.00 0.37 Indigenous 5 Acetone 600.00 222.20 Indigenous 6 Methanol 600.00 222.20 Indigenous 7 Acetone 300.00 111.10 Indigenous 8 Methanolic HCl (10%) 125.00 46.29 Indigenous 9 Activated Carbon 20.00 7.41 Indigenous



9. MAGNESIUM TERTIARY BUTOXIDE



1 Methyl Magnsium Chloride 214.00 535.00 Indigenous 2 THF 2769.30 6923.25 Indigenous 3 Tert-Butanol 200.00 500.00 Indigenous

10. METFORMIN HYDROCHLORIDE



1 Dimethyl amine Hcl 126.00 840.00 Indigenous 2 N-Cyano guanidine 130.00 866.67 Indigenous 3 Xylene 300.00 2000.00 Indigenous 4 Activated carbon 2.00 13.33 Indigenous 5 Hyflow 1.00 6.67 Indigenous 6 Methanol 100.00 666.67 Indigenous

11. METHYL MAGNESIUM CHLORIDE



1 Magnesium Metal 974.00 216.55 Indigenous 2 Methyl Chloride 2026.00 450.45 Indigenous 3 THF 1270.00 282.36 Indigenous

12. N, N-DIMETHYL PROPYL MAGNESIUM CHLORIDE



1 (3-Chloro-propyl)-dimethyl-amine 417.00 556.00 Indigenous

2 Magnesium turnings 84.00 112.00 Indigenous 3 EDB 1.00 1.33 Indigenous 4 Iodine 0.20 0.27 Indigenous 5 THF 1000.00 1333.33 Indigenous 6 Toluene 1000.00 1333.33 Indigenous



13. OMEPRAZOLE



1 3,5-Lutidine 33.00 220.00 Indigenous

2 2-Mercapto-5-methoxy Benzimidazole 53.50 356.67 Indigenous

3 Acetic acid 25.00 166.67 Indigenous 4 Acetone 250.00 1666.67 Indigenous 5 Ammonium hydroxide 22.00 146.67 Indigenous 6 Dimethyl sulphate 38.30 255.33 Indigenous 7 Hydrogen Peroxide 23.00 153.33 Indigenous 8 Methanol 750.00 5000.00 Indigenous 9 Nitric acid 19.50 130.00 Indigenous

10 Sodium hydroxide 24.30 162.00 Indigenous 11 Sodium methoxide 16.40 109.33 Indigenous 12 Stage-1 252.00 1680.00 Indigenous 13 Thionyl Chloride 36.00 240.00 Indigenous 14 Toluene 1000.00 6666.67 Indigenous



14. PANTOPRAZOLE SODIUM



1 Maltol 66.00 165.00 Indigenous

2 5-diFluoromethoxy-2-mercaptobenzimidazole


3 Acetic acid 40.00 100.00 Indigenous 4 Acetic Anhydride 172.00 430.00 Indigenous 5 Acetone 1000.00 2500.00 Indigenous 6 Activated Carbon 10.00 25.00 Indigenous 7 Ammonia 9.00 22.50 Indigenous 8 Ammonium Carbonate 50.00 125.00 Indigenous 9 Ammonium Chloride 25.00 62.50 Indigenous

10 Ammonium hydroxide 35.50 88.75 Indigenous 11 Chloroform 1050.00 2625.00 Indigenous 12 Dimethyl sulphate 33.00 82.50 Indigenous 13 Hydrogen peroxide 17.00 42.50 Indigenous 14 MDC 900.00 2250.00 Indigenous 15 Methanol 875.00 2187.50 Indigenous 16 Methylene dichloride 1300.00 3250.00 Indigenous 17 Phosphorous oxy chloride 26.00 65.00 Indigenous 18 Potassium carbonate 36.00 90.00 Indigenous 19 Sodium Hydroxide 40.00 100.00 Indigenous 20 Sodium Hydroxide flakes 20.00 50.00 Indigenous 21 Sodium hypochlorite 37.00 92.50 Indigenous 22 Sodium methoxide 27.00 67.50 Indigenous 24 Thionyl chloride 60.00 150.00 Indigenous 25 Toluene 800.00 2000.00 Indigenous

15. PHENYL MAGNESIUM CHLORIDE



1 Magnesium turnings 180.00 90.00 Indigenous 2 Chlorobenzene 820.00 410.00 Indigenous 3 THF 800.00 400.00 Indigenous



16. QUETIAPINE FUMARATE



1 2-Aminbiphenylsulphate 140.00 116.67 Indigenous 2 Acetone 400.00 333.33 Indigenous 3 Chloro ethoxy ethanol 59.00 49.17 Indigenous 4 Fumaric acid 85.00 70.83 Indigenous 5 Hydrogen gas 1.02 0.85 Indigenous 6 Methanol. 400.00 333.33 Indigenous 7 Phenyl chloro fumarate 118.50 98.75 Indigenous 8 phosphoric acid 46.70 38.92 Indigenous 9 Piperazine 44.00 36.67 Indigenous

10 Toluene 1150.00 958.33 Indigenous

17. RABEPRAZOLE SODIUM

S. No Raw Material Used /Batch

in Kgs Used/ Day in

Kgs Source

1 2,3-Lutidine 46.00 76.67 Indigenous 2 2-Mercaptobenzimidazole 53.00 88.33 Indigenous 3 3-Methoxy-1-Propanol 43.00 71.67 Indigenous 4 Acetic acid 6.00 10.00 Indigenous 5 Acetic anhydride 39.00 65.00 Indigenous 6 Acetone 150.00 250.00 Indigenous 7 Activated Carbon 10.00 16.67 Indigenous 8 Ammonium hydroxide 12.50 20.83 Indigenous 9 DMSO 200.00 333.33 Indigenous

10 Hydrochloric acid 20.00 33.33 Indigenous 11 Hydrogen Peroxide (50%) 33.00 55.00 Indigenous 12 Isopropyl Alcohol 300.00 500.00 Indigenous 13 MDC 1350.00 2250.00 Indigenous 14 MMA in Methanol 10.00 16.67 Indigenous 15 Nitric acid 38.00 63.33 Indigenous 16 Sodium hydro sulphate 12.00 20.00 Indigenous 17 Sodium Hydroxide 43.50 72.50 Indigenous 18 Sodium Hypochlorite (8%) 327.00 545.00 Indigenous 19 Sodium Sulphate 10.00 16.67 Indigenous 20 Stage-1 515.00 858.33 Indigenous 21 Thionyl Chloride 53.00 88.33 Indigenous 22 Toluene 1350.00 2250.00 Indigenous



18. SODIUM METHOXIDE



1 Sodium hydroxide 1482.00 1235.00 Indigenous 2 Methanol 1700.00 1416.67 Indigenous

19. SODIUM TERT BUTOXIDE



1 Sodium 141.18 188.24 Indigenous 2 Tert-Butanol 650.00 866.67 Indigenous

20. TELMISARTAN



1 Methyl-4-methyl-1,1-biphenyl-2-carboxylate 57.00 57.00 Indigenous

2 1,3-dibromo-5,5-dimethyl imidazolidine-2,4-dione 72.00 72.00 Indigenous

3 Acetic acid 80.00 80.00 Indigenous 4 Acetone 450.00 450.00 Indigenous 5 Activated carbon 10.00 10.00 Indigenous 6 Azo bis isobutyronitrile 2.90 2.90 Indigenous 7 Chloroform 320.00 320.00 Indigenous 8 Hydrochloric acid 81.00 81.00 Indigenous 9 MDC 1200.00 1200.00 Indigenous

10 Methanol 2695.00 2695.00 Indigenous 11 Methanolic ammonia 50.00 50.00 Indigenous

12 Methyl-4-(butyramido)-3-methyl-5-nitrobenzene 73.00 73.00 Indigenous

13 n-Hexane 100.00 100.00 Indigenous

14 N-Methylbenzene-1,2-diamine 32.00 32.00 Indigenous

15 Palladium carbon(Wet 5% MC) 3.00 3.00 Indigenous

16 Phosphoric acid 90.00 90.00 Indigenous 17 Potassium hydroxide 33.00 33.00 Indigenous 18 Sodium hydroxide 120.60 120.60 Indigenous 19 Sodium meta bisulphate 4.30 4.30 Indigenous



Annexure - VIII

LIST OF BY -PRODUCTS

S. No Name of the Product Name of the By- Product

Quantity In Kg/Day

1 Ciprofloxacin Hydrochloride Piperazine Hydrochloride 41.00

2 N-Butyl Lithium Lithium Chloride 171.00 3 Ritonovir 4-Nitro phenol 46.00



Annexure - IX

WASTE WATER DETAILS

S. No Purpose Effluent In KLD

1 Process 52.39 2 Washings 2.00 3 Boiler Blow down 8.50 4 Cooling towers Blow down 26.00 5 DM Plant Regeneration 2.00 6 Scrubbing system 2.00 7 Domestic 2.00 Total 95.00

HTDS & LTDS DETAILS

Unit HTDS KLD

LTDS KLD

Effluent Generation

in KLD

Treatment Method

Process 29.98 22.41 52.39 HTDS Effluent after neutralization, filtration sent to MEE. LTDS effluents along with MEE condensate will be sent to Biological treatment and finally to RO system RO Rejects to MEE system and RO permeate to reuse; MEE residue to ATFD for drying.

Washings 0.00 2.00 2.00 Boiler Blow down 8.50 0.00 8.50 Cooling towers Blow down 26.00 0.00 26.00 DM Plant Regeneration 2.00 0.00 2.00

Scrubbing system 2.00 0.00 2.00

Domestic 0.00 2.00 2.00 Septic tank followed by soak pit

Total 68.48 26.41 95.00