Fast Claisen condensation reaction optimization in a continuous flow reactor

Abstract

In our previous study, we described the batch synthesis of CPL304110, an innovative pan-FGFR inhibitor. Herein, we transferred the Claisen condensation reaction, one of the synthesis steps to a continuous flow reactor. A simple solvent switch from ethanol to tetrahydrofuran shortened the original reaction time from 20 h to 10 min. With the use of the design of experiment method and program Statistica®, we optimized reaction parameters and increased the reaction yields from 73 to 84% with greatly shortened reaction times (20 h vs. 2 min), improved productivity (74.4 g h−1), and increased space–time yield (3720 kg h−1 m−3). Graphical abstract: [Figure not available: see fulltext.]