A sequential multistep process for the fully mechanochemical, one-pot synthesis of the antiepileptic drug rufinamide

Mechanochemistry is a powerful tool to develop environmentally benign syntheses of active pharmaceutical ingredients. In this context, we report here the synthesis of the anti-epileptic agent rufinamide through a one-pot sequential multi-component approach, which was fully carried out applying a ball milling method. This solid-state synthesis of rufinamide has proved to be more efficient in terms of sustainability than the equivalent conventional synthetic process in solution. The mechanochemical method presents several advantages such as shorter reaction times, pot economy, the absence of external heating and solvent use. The ball milling-based synthesis of rufinamide has shown excellent green metrics and it is in agreement with several principles of Green Chemistry.