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.

No abstract