Department of Process Research, Merck Frosst Canada, Kirkland, Quebec, Canada.
J Org Chem. 2011 Mar 4;76(5):1436-9. doi: 10.1021/jo1018574. Epub 2011 Feb 1.
In this report, we disclose our findings regarding the remarkable effect of a low-level impurity found in the solvent used for a ruthenium-catalyzed direct arylation reaction. This discovery allowed for the development of a robust and high-yield arylation protocol that was demonstrated on a multikilogram scale using carboxylate as the cocatalyst. Finally, a practical, scalable, and chromatography-free synthesis of the biaryl core of Anacetrapib is described.
在本报告中，我们披露了我们在研究中发现的一个有趣的现象，即在用于钌催化直接芳基化反应的溶剂中存在的低水平杂质会产生显著的影响。这一发现促使我们开发了一种稳健、高产的芳基化方法，该方法使用羧酸盐作为共催化剂，在多公斤规模上得到了验证。最后，我们还描述了一种实用的、可规模化的、无需色谱分离的安塞曲匹（Anacetrapib）的联芳基核心合成方法。
