Highly efficient asymmetric synthesis of sitagliptin

…, S Krska, T Rosner, B Simmons, J Balsells…

Index: Hansen, Karl B.; Hsiao, Yi; Xu, Feng; Rivera, Nelo; Clausen, Andrew; Kubryk, Michele; Krska, Shane; Rosner, Thorsten; Simmons, Bryon; Balsells, Jaume; Ikemoto, Nori; Sun, Yongkui; Spindler, Felix; Malan, Christophe; Grabowski, Edward J. J.; Armstrong III, Joseph D. Journal of the American Chemical Society, 2009 , vol. 131, # 25 p. 8798 - 8804

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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, ...