An Alternative Scalable Process for the Synthesis of the Key Intermediate of Omarigliptin

详细信息    查看全文

• 作者：Guodong Sun ; Mingjie Wei ; Zhonghua Luo ; Yongjun Liu ; Zhijun Chen ; Zhongqing Wang
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：December 16, 2016
• 年：2016
• 卷：20
• 期：12
• 页码：2074-2079
• 全文大小：380K
• ISSN：1520-586X

文摘

An alternative scalable process for the synthesis of the key intermediate of omarigliptin is described. The asymmetric synthesis relies on the initial diastereoselective alkylation and subsequent aluminum-catalyzed substrate-controlled Meerwein–Ponndorf–Verley reduction. A highly regioselective 5-exo-dig iodocyclization followed to afford 11b, which was then subjected to ring-opening cycloetherification to give product 1 with >99:1 dr and >99% ee in 31.2% overall yield in nine steps. This synthetic strategy has been successfully applied for multikilogram scale production.