Solving Gas–Liquid\nMixing-Induced Clogging\nin Continuous-Flow Hydrogenation Synthesis of an API Intermediate

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