Continuous Flow Synthesis of 4-methyl-3-oxo-n-phenyl-pentanamide

Graphical Atorvastatin calcium is a pivotal pharmaceutical for the treatment of primary hypercholesterolemia, with the reaction between isobutyl acetate and aniline being a crucial step. By employing continuous flow synthesis technology, we achieved a yield of 94 % within a residence time of 15 minutes. Simultaneously, kinetic studies and CFD calculations were conducted. Subsequently, we conducted further reaction investigations and designed a continuous system. 4-methyl-3-oxo-n-phenyl-pentanamide, as a crucial component of atorvastatin calcium, often generates a large amount of by-products in conventional synthesis. Here, we first developed a continuous microflow system for the continuous flow synthesis of 4-methyl-3-oxo-n-phenyl-pentanamide. Compared to traditional batch reactors, the reaction time was reduced by 1/12 in the microreactor. Using this device, the kinetic parameters of the reaction were determined, and a reaction kinetics model was established to investigate the effects of channel geometry and material inlet velocity on the entire reaction system. Furthermore, we studied the subsequent reactions and successfully established a fully continuous synthesis device, where the two-step continuous flow chemical reactions were achieved at 40 minutes and a total yield of 32 %.