A new synthetic route for the preparation of pregabalin

Abstract

We reported the synthesis of (S)-pregabalin in a five-step sequence with 20% overall yield. As a modification of the previously developed route, a Michael addition between CH₃NO₂ and chiral oxaoxazolidinone was employed as a key operation for introducing the methyleneamino group, which allowed avoiding the use of toxic cyanide reagent and led to enantiomerically pure product (>99% ee) after the recrystallization in appropriate solvent.

Graphical Abstract

Keywords:

• Cyanide reagent
• Michael addition
• oxaoxazolidinone
• pregabalin
• recrystallization

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by the National Science and Technology Major Project [No. 2018ZX09711002-002-009], the National Natural Science Foundation of China [No. 81703358], and Science and Technology Commission of Shanghai Municipality [Nos. 17431903900, 18QB1404200].