Enantioselective organocatalysis in microreactors: Continuous flow synthesis of a (S)-pregabalin precursor and (S)-warfarin

Abstract

Continuous flow processes have recently emerged as a powerful technology for performing chemical transformations since they ensure some advantages over traditional batch procedures. In this work, the use of commercially available and affordable PEEK (Polyetheretherketone) and PTFE (Polytetrafluoroethylene) HPLC (High Performance Liquid Chromatography) tubing as microreactors was exploited to perform organic reactions under continuous flow conditions, as an alternative to the commercial traditional glass microreactors. The wide availability of tubing with different sizes allowed quickly running small-scale preliminary screenings, in order to optimize the reaction parameters, and then to realize under the best experimental conditions a reaction scale up for preparative purposes. The gram production of some Active Pharmaceutical Ingredients (APIs) such as (S)-Pregabalin and (S)-Warfarin was accomplished in short reaction time with high enantioselectivity, in an experimentally very simple procedure.