An Asymmetric Synthesis of Clopidogrel Hydrogen Sulfate

作者：Sashikanth Suthrapu; Raju Veeramalla; Somaiah Sripathi; Rao Peddi Srinivasa; Reddy Karnati Venugopal^*

来源：Synthesis, 2013, 45(5): 621-624.

DOI：10.1055/s-0032-1316852

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

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.

• 出版日期2013-3