Integration of Liquid–Liquid Biphasic Flow Alkylation and Continuous Crystallization Using Taylor Vortex Flow Reactors

• Masahiro Hosoya^a
• Masashi Tanaka^a
• Atsushi Manaka^a
• Shogo Nishijima^a
• Naoki Tsuno^a

• ^a API R&D Laboratory, CMC R&D Division, Shionogi and Company Ltd., 1-3, Kuise Terajima 2-chome, Amagasaki, Hyogo 660-0813, Japan

This work established the integration of a continuous flow reaction and continuous crystallization using Taylor vortex flow reactors. We previously developed liquid–liquid biphasic flow alkylation using a Taylor vortex flow reactor, which is a scalable flow reactor with high mixing efficiency. To maximize the efficiency of this methodology, we evaluated process parameters and instrumental parameters, such as the rotating speed and tilt of the reactor, and optimized the reaction conditions. As a result, the throughput increased more than 20-fold compared to our previous work, and a long-run experiment verified its robustness. Liquid–liquid biphasic flow alkylation, quenching, phase separation, continuous crystallization, and filtration were integrated by using Taylor vortex flow reactors for both the flow reaction and continuous crystallization. The integrated system using two Taylor vortex flow reactors provided the alkylated product continuously from the solution of the starting material.

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