Process Development of a Triphasic Continuous Flow Suzuki–Miyaura Coupling Reaction in a Plug Flow Reactor

Abstract

We have successfully adapted a Suzuki–Miyaura coupling reaction to a continuous flow process. The reaction was a triphasic mixture involved with two liquid phases that are only partially miscible in addition to the presence of an insoluble catalyst as a solid phase. The reaction required very rapid reaction heat up and mixing, which were difficult to achieve under batch conditions. A plug flow reactor (PFR) equipped with a static mixer was implemented in this continuous flow process, and the heterogenous reaction mixture was well handled, which is attributed to the high velocity flow rates and fast reaction kinetics. The reaction was successfully carried out on a 1.6 kg scale to give 80% isolated yield of the product with superior reaction high-performance liquid chromatography profile to the batch process.