Multi-step solvent-free 3 m2 footprint pilot miniplant for the synthesis of annual half-ton rufinamide precursor

The development of a pilot-scale synthesis of the rufinamide precursor in flow chemistry is reported. Complex steps such as Taylor-flow, segmented flow, and high-temperature processing at high pressure (high-p,T) are successfully combined, overcoming the mixing and heat transfer issues of the scale-up. The cascaded multistep process operates essentially solvent-free in just 3 m2 giving a productivity of 47 g/h (>400 kg/year), which increases in a factor of 7 the lab-scale productivity previously reported as a scale-up proof-of-concept. The publication also includes an economic study of the feasible implementation of this technology for a possible manufacturer, as well as an outline on business development strategies how to implement such kind of disruptive technology.