A continuous flow process for biaryls based on sequential Suzuki–Miyaura coupling and supercritical carbon dioxide extraction

Abstract

We report a continuous flow process for biaryls consisting of a packed-bed reactor and a rapid extraction system. Continuous extraction with supercritical carbon dioxide (scCO₂) was applied to a Suzuki–Miyaura coupling reaction mixture, which is typically challenging to connect with a continuous purification system. The flow synthesis module was optimized based on kinetic studies and yielded an aqueous ethanol solution of the target biaryls in quantitative yield; subsequently, continuous extraction with scCO₂ to separate the biaryls and co-produced salts was carried out. This continuous process gave the desired biaryls in high yields and purities with almost no salts.