Design and Comparison of Tubular and Pipes-in-Series Continuous Reactors for Direct Asymmetric Reductive Amination

A high pressure, high temperature direct asymmetric reductive amination (DARA) reaction was run in three different continuous reactor types; coiled tubes, horizontal pipes in series, and vertical pipes in series. The goal of this work was to design a continuous reactor scalable to large volumes needed for commercial scale manufacturing. With about 4000:1 substrate to dissolved catalyst ratio, the DARA reaction achieved about 90% conversion to desired product in 12 h, about 8% conversion to undesired ketone, and about 95% ee, in batch and in all 3 types of continuous reactors. The 3 continuous reactors were compared on the basis of vapor/liquid mass transfer rates, overall pressure drop, and axial dispersion. Vertical pipes in series were selected as the best option because of scalability and vapor/liquid mass transfer rates, although horizontal pipes had lower pressure drop and less potential for surging.