An Asymmetric Synthesis of Clopidogrel Hydrogen Sulfate

Abstract

An asymmetric synthesis of (S)-(+)-clopidogrel hydrogen sulfate has been developed through application of a Strecker reaction with [(1S)-1-(4-methoxyphenyl)ethyl]amine hydrochloride as a chiral auxiliary. Addition of 2-chlorobenzaldehyde to a solution of sodium cyanide and [(1S)-1-(4-methoxyphenyl)ethyl]amine hydrochloride­ gave diastereoisomerically pure (2S)-(2-chlorophenyl){[(1S)-1-(4-methoxyphenyl)ethyl]amino}acetonitrile hydro­chlor­ide. Cleavage of the chiral auxiliary and concomitant hydrolysis of the nitrile group then gave enantiomerically pure (2S)-2-(2-chlorophenyl)glycine hydrochloride, a key intermediate for (S)-(+)-clopidogrel.

Key words

asymmetric synthesis - heterocycles - Strecker reaction - cyclizations - chiral auxiliaries - stereoselective synthesis

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