Micro-total process system machine (mu-TPSM) for rapid synthesis of antiretroviral darunavir

Batch processes show great potential in antiretroviral darunavir (DRV) synthesis, but the longer process time, expensive catalyst, shortage of skilled manpower, laborious post-synthetic work-up, transport of one intermediate from one place to another, and need for maintaining expensive storage inventory are some major limitations. Herein, we report the first-ever individual continuous flow sequence involving 7 steps and an integrated micro-total process system machine (mu-TPSM) for the last 4 steps of API DRV synthesis. Employing this mu-TPSM, DRV could be synthesized within 41 min of total residence time with a 71% isolated yield, and an output of 0.8 g h(-1). The use of RANEY (R)-Ni instead of palladium on carbon renders the process more affordable.