Continuous-Flow Supercritical CO₂ Platform for In-Situ Synthesis and Purification of Small Molecules for Drug Discovery

The use of supercritical CO2 (scCO2) as an enabling technology paves the way for an efficient in-line integration of the synthesis and purification of organic molecules. The scCO2 platform presented here provides a streamlined process to produce a diverse family of triazoles, common drug precursors, by 1,3-dipolar copper-catalyzed azide-alkyne cycloaddition (CuAAC, Huisgen reaction), also decreasing the environmental impact by significantly reducing the use of traditional solvents. To further exemplify the potential of this scCO2 platform, the synthesis and purification of rufinamide, a drug used to treat seizures associated with Lennox–Gastaut syndrome, is also reported.