Shinde Anand H, Sayini Ramakrishna, Singh Piyal, Burns Justina M, Ahmad Saeed, Laidlaw G Michael, Gupton B Frank, Klumpp Douglas A, Jin Limei
Medicines for All Institute, Virginia Commonwealth University, Richmond, Virginia 23284-3068, United States.
J Org Chem. 2025 Jan 10;90(1):471-478. doi: 10.1021/acs.joc.4c02380. Epub 2024 Dec 16.
Herein, we describe a new seven-step approach to prepare ()-1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl)ethan-1-amine (()-) from the inexpensive 2-(3,5-difluorophenyl)acetic acid. The key steps in the sequence include (1) the Weinreb amide-based ketone synthesis to provide an entry point to the core structure; (2) simple functional group transformations to afford the racemic amine -; and (3) dynamic kinetic resolution (DKR) to access the chiral amine ()-. This seven-step process delivered the enantiopure amine ()- in an overall isolated yield of approximately 15%. The process was demonstrated on a decagram scale, and the process requires no chromatographic purifications. Single-crystal X-ray crystallography measurements verified the chiral amine structure and absolute configuration.
在此，我们描述了一种从廉价的2-(3,5-二氟苯基)乙酸制备()-1-(3,6-二溴吡啶-2-基)-2-(3,5-二氟苯基)乙-1-胺()的新的七步方法。该序列中的关键步骤包括：(1) 基于Weinreb酰胺的酮合成，以提供进入核心结构的切入点；(2) 简单的官能团转化以得到外消旋胺-；以及(3) 动态动力学拆分(DKR)以获得手性胺()。这个七步过程以大约15%的总分离产率得到了对映体纯的胺()。该过程在十克规模上得到了验证，并且该过程不需要色谱纯化。单晶X射线晶体学测量验证了手性胺的结构和绝对构型。
