Continuous Flow Synthesis of Amides in Bio-Derived Solvent GVL

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<sup>-1</sup> and 0.99 g day<sup>-1</sup>. The finding of our work aligned with green chemistry principles should result in its adoption by the chemistry community.