Nanofiltration-Enabled InSitu Solvent and Reagent Recycle for Sustainable Continuous-Flow Synthesis

Solvent usage in the pharmaceutical sector accounts for as much as 90% of the overall mass during manufacturing processes. Consequently, solvent consumption poses significant costs and environmental burdens. Continuous processing, in particular continuous-flow reactors, have great potential for the sustainable production of pharmaceuticals but subsequent downstream processing remains challenging. Separation processes for concentrating and purifying chemicals can account for as much as 80% of the total manufacturing costs. In this work, a nanofiltration unit was coupled to a continuous-flow rector for insitu solvent and reagent recycling. The nanofiltration unit is straightforward to implement and simple to control during continuous operation. The hybrid process operated continuously over sixweeks, recycling about 90% of the solvent and reagent. Consequently, the E-factor and the carbon footprint were reduced by 91% and 19%, respectively. Moreover, the nanofiltration unit led to a solution of the product eleventimes more concentrated than the reaction mixture and increased the purity from 52.4% to 91.5%. The boundaries for process conditions were investigated to facilitate implementation of the methodology by the pharmaceutical sector.