Development of a Large-Scale Copper(I)/TEMPO-Catalyzed Aerobic Alcohol Oxidation for the Synthesis of LSD1 Inhibitor GSK2879552
Development of a Large-Scale Copper(I)/TEMPO-Catalyzed Aerobic Alcohol Oxidation for the Synthesis of LSD1 Inhibitor GSK2879552
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DOI：
10.1021/acs.organomet.8b00546
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发表时间：
2019-01-14
期刊：
影响因子：
2.8
通讯作者：
Sanganee, Mahesh J.
中科院分区：
文献类型：
--
作者：
Ochen, Augustine;Whitten, Robert;Sanganee, Mahesh J.
采用CuI和克里思（2，2，6，6-四甲基哌啶-1-氧基）催化剂体系，通过有氧氧化反应，将醛转化为LSD 1抑制剂。在这份报告中，动力学信息被用来了解影响催化剂性能和醛产率的许多关键副产物的产生。洞察这些副产品的形成影响因素。该Cu-I/克里思催化剂促进起始脂肪醇在1-2小时内的快速转化，其表观零级动力学对于使用该催化剂体系的该底物类别是前所未有的。催化剂组分和反应溶剂的工艺优化导致在间歇式反应器中用鼓泡空气成功地将该氧化放大400 g。
An improved process to an aldehyde en route to an LSD1 inhibitor was developed using an aerobic oxidation with a CuI and TEMPO (2,2,6,6-tetramethylpiperdine 1-oxyl) catalyst system. In this report, kinetic information is utilized to understand the generation a of number of key byproducts that affect catalyst performance and aldehyde yield. Insight into factors affecting the formation of these byproducts is presented. This Cu-I/TEMPO catalyst facilitates rapid conversion of the starting aliphatic alcohol in 1-2 h with apparent zero-order kinetics unprecedented for this substrate class with this catalyst system. Process optimization of catalyst components and reaction solvent led to the successful 400 g scale-up of this oxidation with bubbling air in a batch reactor.