Solving Gas–Liquid Mixing-Induced Clogging in Continuous-Flow Hydrogenation Synthesis of an API Intermediate

A simple and widely applicable technique to avoid precipitation-induced clogging in continuous-flow processes involving gas and liquid reagents (such as hydrogenations) has been developed. Management of solid compounds poses one of the largest scale-up risks in the flow manufacturing of pharmaceuticals and fine chemicals. As noted in this study, compounds with limited solubility in low-boiling solvents can be susceptible to precipitation when mixed with a gas stream in a standard tee-mixer. The prescribed technique, whereby the gas stream is prewetted with a solvent prior to contacting with the feed solution, has been successfully applied both in lab and scale-up platforms to enhance the stable (clog-free) operating run time of continuous-flow synthesis of an active pharmaceutical ingredient (API) intermediate from minutes to days.