CHEE 323 J.S. Parent 1

Enantioselective Hydrogenation-Design Exercise #2

Despite its rather severe side-effects, L-Dopa (3,4-dihydroxyphenylalanine) is the most widely used drug for the treatment of Parkinson’s disease.

It is prepared commerciallythrough a multi-step synthesisthat includes an enantioselectivehydrogenation of -acylaminoacrylicacid derivative

CHEE 323 J.S. Parent 2

Mission Impossible?

Your mission, should you choose to pass CHEE 323, is to develop a preliminary design for the production of a fluorinated L-dopa derivative that is about to be tested in clinical trials.

Your firm has been contracted to carry out the hydrogenation process, as shown below:

The contract deliverables include 750 kg of material to be provided in 6 months. Given that you are given 1 month to complete the design and approximately 3 months time will be needed to commission equipment, your process must yield 750 kg in just 2 months.

OMe

AcO

CCCO2H

NHAcH

FH2

OMe

AcO

CCCO2H

NHAc

HF

H2

[Rh(R,R-DIPAMP)(NOR)]+BF4-

CHEE 323 J.S. Parent 3

Mission Impossible?

Product Specifications: Isolated product to be fully hydrogenated, with a minimum

99% enantiomeric excess “Lowest cost alternative” from an overall process

perspective.

OMe

AcO

CCCO2H

NHAcH

FH2

OMe

AcO

CCCO2H

NHAc

HF

H2

[Rh(R,R-DIPAMP)(NOR)]+BF4-

CHEE 323 J.S. Parent 4

Design Teams

Catalytic Chemist: provide a reaction mechanism (best available knowledge)

and a rate equation suitable for design purposes address selectivity of the process advise on process conditions and estimate reaction rate

Reactor Design Engineer: specify reactor(s) configuration and size address mass and heat transfer design issues propose a reaction monitoring and control scheme develop a product purification scheme if the design criteria

cannot be met by hydrogenation alone.

CHEE 323 J.S. Parent 5

Preliminary Design Report

All teams will submit a nine page (max) design report: Each team member contributes a maximum of three pages to

the report, detailing their assigned contributions to the project.

The team will prepare a process flowsheet, specifying reactant and product handling and isolation steps. Details will be written up in two-page summary.

The final page of the report will be prepared jointly. It will state the limitations of the design and make specific recommendations regarding information needed to proceed with the design process.

Data and process schematics can be presented in Appendices where appropriate. However, all data should be presented clearly and concisely.

CHEE 323 J.S. Parent 6

Today’s Exercise

The design process will start with an individual group brainstorming session.

Propose a series of processes that may accomplish the assigned task.

Discuss what reactor configurations are most appropriate Detail the criteria by which a catalyst and reaction conditions

may be selected …

At the end of class, each group will submit a request for information on every design element (overall process, catalyst technology, reactor design).

No less than 2 and no more than 5 questions from each group member (for now)

Depending on the questions, direct information may be provided or literature pertaining to the question could be furnished.