Invention and implementation of technologies for continuous flow synthesis

In this thesis, I have optimized a synthesis of rufinamide an important epilepsy medication. This convergent synthesis generates two reactive intermediates in situ (aryl azide and propiolamide) and then combines them in a regioselective click reaction utilizing copper tubing as the catalyst. Next, I have optimized a synthesis of nicardipine which is prescribed to treat high blood pressure. The nature of the project required that the final product be relatively pure (>90 %) so that the final product could be crystallized from the reaction mixture. Nicardipine was synthesized in three steps, but in two flow reactors where one of the reactors induced two steps. The reaction mixture was then purified using two in-line aqueous extrations. First, the reaction stream was washed with HCl to produce the salt of nicardipine and wash away polar compounds. Then, the product is extracted into the aqueous layer by using a 1:1 water DMSO mixture.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Russell, Mary Grace.

Advisor dc:contributor.advisor

• Timothy F. Jamison.

• Chemistry.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/127715

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/127715