A Practical and Efficient Preparation of (S)‐2‐Benzylsuccinic Acid: A Key Acid Synthon of KAD‐1229

Abstract

This report describes a practical and an efficient synthesis of (S)‐2‐benzylsuccinic acid, which was employed as a key intermediate for hypoglycemic KAD‐1229 by means of asymmetric alkylation of N‐acylsultam. The condensation of D‐(−)‐camphorsultam with 3‐phenylpropionyl chloride gave N‐acylsultam 1. N‐acylsultam 1 reacted with 1.1 equimolar amount of sodium amide base to form chiral enolate, followed by alkylation with tert‐butyl bromoacetate to afford 2. Cleavage of ester and saponification with H₂O₂–LiOH provided the desired compound 5 with excellent yield and high optical purity.

Keywords:

• KAD‐1229
• (S)‐2‐Benzylsuccinic acid
• Camphorsultam