Process Research and Development of an Enantiomerically Enriched Allyic Amine, One of the Key Intermediates for the Manufacture of Synthetic Tetracyclines

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• 作者：Wu-Yan Zhang ; Philip C. Hogan ; Chi-Li Chen ; John Niu ; Zhimin Wang ; Danny Lafrance ; Olga Gilicky ; Nicholas Dunwoody ; Magnus Ronn
• 刊名：Organic Process Research & Development
• 出版年：2015
• 出版时间：November 20, 2015
• 年：2015
• 卷：19
• 期：11
• 页码：1784-1795
• 全文大小：444K
• ISSN：1520-586X

文摘

A robust, cost-effective, and high yielding manufacturing process for enantiomerically enriched (S)-allylic amine 3, a key intermediate for fully synthetic tetracyclines have been developed. Two novel and scalable asymmetric vinylations resulting in high-to-excellent stereoselectivity have been developed for the key step. The final product is purified by an efficient crystallization of a class="smallcaps">l-tartaric salt. The process described has been used to manufacture 鈭?50 kg of the tartaric salt of 3 with 99.0% ee in 8 steps (35% overall yield) from cheap and readily available dimethyl maleate.