Synthetic Improvements in the Preparation of Clopidogrel

Abstract

Synthetic improvements in the preparation of clopidogrel are described. The synthesis was accomplished in four steps or one-pot in above 70% overall yield. The process featured PTC catalyzed alkaline hydrolysis of the key intermediate 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetonitrile and highly effective kinetic resolution of racemic clopidogrel using l-camphorsulphonic acid in toluene and has been successfully used in a 50-kg pilot test.