A convenient and highly enantioselective synthesis of (S)-2-pipecolic acid: an efficient access to caine anesthetics

Abstract

A novel and enantioselective synthesis of (S)-2-pipecolic acid (5) has been achieved from Oppolzer’s sultam (1) and ethyl N-(diphenylmethylene)glycinate (2) as readily available starting materials. The highly stereoselective alkylation of chiral glycine intermediate (3) with 1,4-dibromobutane afforded the key backbone of (S)-2-pipecolic acid (5) in one-step that was utilized into the preparation of the local anesthetics mepivacaine, ropivacaine and bupivacaine.

Graphical Abstract

Keywords:

• Oppolzer’s sultam
• N-(diphenylmethylene)glycinate
• (S)-2-pipecolic acid
• caine anesthetics
• asymmetric synthesis

Additional information

Funding

We are grateful to the National Natural Science Foundation of China [21877099], and Zhejiang Provincial College Students’ Science and Technology Innovation Project and the National Undergraduate Innovative Program [202010337038].