Synthesis of a Precursor to Sacubitril Using Enabling Technologies

详细信息    查看全文

• 作者：Shing-Hing Lau ; Samuel L. Bourne ; Benjamin Martin ; Berthold Schenkel ; Gerhard Penn ; Steven V. Ley
• 刊名：Organic Letters
• 出版年：2015
• 出版时间：November 6, 2015
• 年：2015
• 卷：17
• 期：21
• 页码：5436-5439
• 全文大小：361K
• ISSN：1523-7052

文摘

An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by integrating machine-assisted methods with batch processes, this procedure allows a safe and rapid production of the key intermediates which are promptly transformed to the target molecule (3路HCl) over 7 steps in 54% overall yield.