Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: A key intermediate for dipeptidyl peptidase IV inhibitors

Abstract

An alternative and practical synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile was achieved. Reaction of L-proline with chloroacetyl chloride was followed by conversion of the carboxylic acid moiety of the resulting N-acylated product into the carbonitrile via the corresponding amide intermediate. The synthesized pyrrolidine derivative was utilized to prepare DPP-IV inhibitor Vildagliptin.

Keywords

• amides
• DPP-IV inhibitors
• L-proline
• N-acylation
• 2(S)-cyanopyrrolidine