Highly Enantioselective Synthesis of Sitagliptin
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 sc...
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| Veröffentlicht in: | Asian journal of organic chemistry 2020-02, Vol.9 (2), p.189-191 |
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| container_title | Asian journal of organic chemistry |
| container_volume | 9 |
| creator | Khopade, Kishor V. Sen, Anirban Birajdar, Rajkumar S. Paulbudhe, Uday P. Kavale, Dattatry S. Shinde, Prashant S. Mhaske, Santosh B. Chikkali, Samir H. |
| description | 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.
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. |
| doi_str_mv | 10.1002/ajoc.201900709 |
| format | Article |
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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.</description><identifier>ISSN: 2193-5807</identifier><identifier>EISSN: 2193-5815</identifier><identifier>DOI: 10.1002/ajoc.201900709</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>asymmetric hydrogenation ; catalysis ; Enantiomers ; FerroLANE ligands ; Organic chemistry ; Rhodium ; sitagliptin ; Synthesis</subject><ispartof>Asian journal of organic chemistry, 2020-02, Vol.9 (2), p.189-191</ispartof><rights>2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3179-aa5ce59a57fec20c8895f8c70451ff992db68ba0d7398451a5436334ffbeed913</citedby><cites>FETCH-LOGICAL-c3179-aa5ce59a57fec20c8895f8c70451ff992db68ba0d7398451a5436334ffbeed913</cites><orcidid>0000-0002-8442-1480</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fajoc.201900709$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fajoc.201900709$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Khopade, Kishor V.</creatorcontrib><creatorcontrib>Sen, Anirban</creatorcontrib><creatorcontrib>Birajdar, Rajkumar S.</creatorcontrib><creatorcontrib>Paulbudhe, Uday P.</creatorcontrib><creatorcontrib>Kavale, Dattatry S.</creatorcontrib><creatorcontrib>Shinde, Prashant S.</creatorcontrib><creatorcontrib>Mhaske, Santosh B.</creatorcontrib><creatorcontrib>Chikkali, Samir H.</creatorcontrib><title>Highly Enantioselective Synthesis of Sitagliptin</title><title>Asian journal of organic chemistry</title><description>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.
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.</description><subject>asymmetric hydrogenation</subject><subject>catalysis</subject><subject>Enantiomers</subject><subject>FerroLANE ligands</subject><subject>Organic chemistry</subject><subject>Rhodium</subject><subject>sitagliptin</subject><subject>Synthesis</subject><issn>2193-5807</issn><issn>2193-5815</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkNFLwzAQh4MoOOZefS743HlJmiX3OMZ0ymAP0-eQpsmWUdvZdEr_ezsq89F7ueP4fnfwEXJPYUoB2KM51HbKgCKABLwiI0aRp0JRcX2ZQd6SSYwH6EtKpAxHBFZhty-7ZFmZqg11dKWzbfhyybar2r2LISa1T7ahNbsyHNtQ3ZEbb8roJr99TN6flm-LVbrePL8s5uvUcioxNUZYJ9AI6Z1lYJVC4ZWVkAnqPSIr8pnKDRSSo-p3RmR8xnnmfe5cgZSPycNw99jUnycXW32oT03Vv9SMix7IaKZ6ajpQtqljbJzXxyZ8mKbTFPRZjD6L0RcxfQCHwHcoXfcPreevm8Vf9gfeV2ZV</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Khopade, Kishor V.</creator><creator>Sen, Anirban</creator><creator>Birajdar, Rajkumar S.</creator><creator>Paulbudhe, Uday P.</creator><creator>Kavale, Dattatry S.</creator><creator>Shinde, Prashant S.</creator><creator>Mhaske, Santosh B.</creator><creator>Chikkali, Samir H.</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-8442-1480</orcidid></search><sort><creationdate>202002</creationdate><title>Highly Enantioselective Synthesis of Sitagliptin</title><author>Khopade, Kishor V. ; Sen, Anirban ; Birajdar, Rajkumar S. ; Paulbudhe, Uday P. ; Kavale, Dattatry S. ; Shinde, Prashant S. ; Mhaske, Santosh B. ; Chikkali, Samir H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3179-aa5ce59a57fec20c8895f8c70451ff992db68ba0d7398451a5436334ffbeed913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>asymmetric hydrogenation</topic><topic>catalysis</topic><topic>Enantiomers</topic><topic>FerroLANE ligands</topic><topic>Organic chemistry</topic><topic>Rhodium</topic><topic>sitagliptin</topic><topic>Synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khopade, Kishor V.</creatorcontrib><creatorcontrib>Sen, Anirban</creatorcontrib><creatorcontrib>Birajdar, Rajkumar S.</creatorcontrib><creatorcontrib>Paulbudhe, Uday P.</creatorcontrib><creatorcontrib>Kavale, Dattatry S.</creatorcontrib><creatorcontrib>Shinde, Prashant S.</creatorcontrib><creatorcontrib>Mhaske, Santosh B.</creatorcontrib><creatorcontrib>Chikkali, Samir H.</creatorcontrib><collection>CrossRef</collection><jtitle>Asian journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khopade, Kishor V.</au><au>Sen, Anirban</au><au>Birajdar, Rajkumar S.</au><au>Paulbudhe, Uday P.</au><au>Kavale, Dattatry S.</au><au>Shinde, Prashant S.</au><au>Mhaske, Santosh B.</au><au>Chikkali, Samir H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Highly Enantioselective Synthesis of Sitagliptin</atitle><jtitle>Asian journal of organic chemistry</jtitle><date>2020-02</date><risdate>2020</risdate><volume>9</volume><issue>2</issue><spage>189</spage><epage>191</epage><pages>189-191</pages><issn>2193-5807</issn><eissn>2193-5815</eissn><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.
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.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/ajoc.201900709</doi><tpages>3</tpages><orcidid>https://orcid.org/0000-0002-8442-1480</orcidid></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | asymmetric hydrogenation catalysis Enantiomers FerroLANE ligands Organic chemistry Rhodium sitagliptin Synthesis |
| title | Highly Enantioselective Synthesis of Sitagliptin |
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