Abstract

(S)-N-Boc-3-Hydroxyadamantylglycine is a key intermediate of saxagliptin. It was synthesized from 1- adamantanecarboxylic acid to afford 1-acetyladamantane (2), which was converted into 2-(1-adamantyl)-2-oxoacetic acid (3) through oxidation, and then into 1-adamantyl-2-hydroxyimino acetic acid (4) followed by treatment of hydroxylamine hydrochloride, then 4 was reducted and Boc-protected to give N-Boc-adamantylglycine (5), which was oxidized with KMnO4 and treated with a chiral base. Utilizing this route, (S)-N-Boc-3-Hydroxyadamantylglycine was prepared. This work is to elaborate a convenient route to synthesize (S)-N-Boc-3-Hydroxyadamantylglycine and provide a new idea for the synthesis of saxagliptin.

Keywords: Boc-protection, reduction, (S)-N-Boc-3-Hydroxyadamantylglycine, saxagliptin, synthesis, treatment.

Graphical Abstract