Highly Enantioselective Synthesis of Sitagliptin. Issue 2 (17th January 2020)

• Record Type: Journal Article
• Authors: Khopade, Kishor V.; Sen, Anirban; Birajdar, Rajkumar S.; Paulbudhe, Uday P.; Kavale, Dattatry S.; Shinde, Prashant S.; Mhaske, Santosh B.; Chikkali, Samir H.
• Is Part Of: Asian journal of organic chemistry. Volume 9:Issue 2(2020)
• Page Start: 189
• Page End: 191
• Publication Date: 2020-01-17
• Subjects: asymmetric hydrogenation -- FerroLANE ligands -- catalysis -- sitagliptin -- rhodium; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; 547.005
• DOI: 10.1002/ajoc.201900709
• Languages: English
• ISSNs: 2193-5807

Abstract

Abstract: A highly enantioselective synthesis of sitagliptin, a potent DPP‐4 inhibitor, is reported. Explicitly identified chiral FerroLANE ligands in the presence of rhodium catalyze the asymmetric hydrogenation of an enamine to yield sitagliptin with excellent enantioselectivity (98% ee ). The process was scaled up to 5 g and the final product was isolated as a phosphate salt with >99% ee . Abstract : The asymmetric hydrogenation of a precursor enamine to sitagliptin has been investigated and initial screening indicated FerroLANE ligands as suitable candidates. Thus, a Rh‐FerroLANE catalyzed, highly enantioselective (>99%) synthesis of sitagliptin, a potent DPP‐4 inhibitor, has been reported. The synthetic utility of the process has been demonstrated by scaling the reaction to 5 g and by isolating sitagliptin in its stable form.