Highly efficient asymmetric synthesis of sitagliptin

…, C Malan, EJJ Grabowski, JD Armstrong III

Index: Xu, Feng; Armstrong III, Joseph D.; Zhou, George X.; Simmons, Bryon; Hughes, David; Ge, Zhihong; Grabowski, Edward J. J. Journal of the American Chemical Society, 2004 , vol. 126, # 40 p. 13002 - 13009

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Citation Number: 155

Abstract

A highly efficient synthesis of sitagliptin, a potent and selective DPP-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM), has been developed. The key dehydrositagliptin intermediate 9 is prepared in three steps in one pot and directly isolated in 82% yield and> 99.6 wt% purity. Highly enantioselective hydrogenation of dehydrositagliptin 9, with as low as 0.15 mol% of Rh (I)/tBu JOSIPHOS, affords sitagliptin, ...