Continuous Flow Synthesis of Amides in Bio-Derived Solvent GVL

Abstract

Abstract: The amide group is one of the most ubiquitous chemical motifs in the pharmaceutical field. An efficient continuous flow synthesis of amides was achieved by coupling acids with amines using 2-bromo-1-ethylpyridinium tetrafluoroborate (BEP) in the bio-derived “green” solvent γ- valerolactone (GVL). The reaction proceeded under mild reaction conditions (ambient temperature, 1 min) with simple filtration without the need for extensive purification, allowing a safe and ondemand generation of procainamide and VH032-Boc with a productivity of 0.44 g day-1 and 0.99 g day-1. The finding of our work aligned with green chemistry principles should result in its adoption by the chemistry community. other: No