Nanofiltration‐Enabled In Situ Solvent and Reagent Recycle for Sustainable Continuous‐Flow Synthesis

The 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 burden. Continuous processing, in particular continuous-flow reactors have a great potential in the sustainable production of pharmaceuticals but subsequent downstream processing remains challenging. Separation processes for the concentration and purification of 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 in situ solvent and reagent recycle. The nanofiltration unit is straightforward to implement and control in a continuous operation. The hybrid process was continuously operated over 6 weeks recycling about 90% of the solvent and the reagent. Consequently, the E factor and the carbon footprint were reduced by 91% and 19%, respectively. Moreover, the nanofiltration unit concentrated the product 11 times and simultaneously 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.