Carbon‐14 labeling of Saxagliptin (BMS‐477118)

An efficient synthesis of carbon‐14‐labeled Saxagliptin (BMS‐477118) is described. Initial synthesis of the key radiolabeled intermediate (S)‐N‐Boc‐2‐(3′‐hydroxyadamantyl)glycine 2a utilized adamantanemethanol in a 10‐step sequence. To shorten the sequence, 1‐adamantylzinc bromide was reacted with ethyl [1, 2‐14C]oxalyl chloride catalyzed by [1,1′‐bis(diphenylphosphino)ferrocene]dichloropalladium (II). In five steps, 2b was synthesized in an overall yield of 20% based on ethyl [1, 2‐14C]oxalyl chloride. Compound 2b was subsequently converted to [14C] BMS‐477118 in a short sequence.