An Asymmetric Synthesis of Clopidogrel Hydrogen Sulfate

Suthrapu Sashikanth; Veeramalla Raju; Sripathi Somaiah; Peddi Srinivasa Rao; Karnati Venugopal Reddy

doi:10.1055/s-0032-1316852

Synthesis, Table of Contents

Synthesis 2013; 45(5): 621-624
DOI: 10.1055/s-0032-1316852

paper

An Asymmetric Synthesis of Clopidogrel Hydrogen Sulfate

Suthrapu Sashikanth

^aDepartment of Research and Development, Srini Pharmaceuticals Limited, Plot No. 10, Type-C, Road No. 8, Film Nagar, Jubilee Hills, Hyderabad 500 033, Andhra Pradesh, India

,

Veeramalla Raju

^aDepartment of Research and Development, Srini Pharmaceuticals Limited, Plot No. 10, Type-C, Road No. 8, Film Nagar, Jubilee Hills, Hyderabad 500 033, Andhra Pradesh, India

,

Sripathi Somaiah

^aDepartment of Research and Development, Srini Pharmaceuticals Limited, Plot No. 10, Type-C, Road No. 8, Film Nagar, Jubilee Hills, Hyderabad 500 033, Andhra Pradesh, India

,

Peddi Srinivasa Rao

^aDepartment of Research and Development, Srini Pharmaceuticals Limited, Plot No. 10, Type-C, Road No. 8, Film Nagar, Jubilee Hills, Hyderabad 500 033, Andhra Pradesh, India

,

Karnati Venugopal Reddy*

^bDepartment of Chemistry, Osmania University, Tarnaka, Hyderabad 500 007, Andhra Pradesh, India Email: drkvr_ou@yahoo.com Email: kvgr1951@gmail.com

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Abstract

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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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References

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