Scaling Up of Continuous Flow Processes with Gases Using a Tube-in-Tube Reactor: Inline Titrations and Fanetizole Synthesis with Ammonia

The development of a tube-in-tube reactor based on a semipermeable polymer membrane has enabled the efficient transfer of gases into liquid flow streams. In this work we describe the scalability and throughput of this reactor when applied to ammonia gas. This is made possible by a convenient titration method to rapidly assess a wide range of parameters including the liquid and gas configuration, reactor temperatures, flow rates, and solvent polarity. These data are then employed in a scaling-up process affording alkyl thioureas and are ultimately applied to a telescoped procedure leading to the anti-inflammatory agent fanetizole on a multigram scale.