Double Heck Route to a Dibenzoxepine and Convergent Suzuki Cross-Coupling Strategy for the Synthesis of an MR Antagonist

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• 作者：Marvin M. Hansen ; Neil J. Kallman ; Thomas M. Koenig ; Ryan J. Linder ; Rachel N. Richey ; John R. Rizzo ; Jeffrey A. Ward ; Hannah Yu ; Tony Y. Zhang ; David Mitchell
• 刊名：Organic Process Research & Development
• 出版年：2017
• 出版时间：February 17, 2017
• 年：2017
• 卷：21
• 期：2
• 页码：208-217
• 全文大小：477K
• ISSN：1520-586X

文摘

A practical pilot plant convergent synthesis of MR antagonist LY2623091 was established. For synthesis convergence, a vinyl bromide geometric isomer and chiral alaninol derivative were required building blocks. Key to the synthesis route development is a stereoselective synthesis of the E-vinyl bromide via a sequential double Heck reaction, Suzuki–Miyaura cross-coupling of the vinyl bromide, a selective nitro reduction, and a highly sensitive cyanamide hydrolysis to the urea. Improvements in yield and processing were accomplished by two sets of telescoping methods which decreased the manufacturing time and provided purity enhancements.