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

ABSTRACT

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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Mechanochemical synthesis
• solid-state chemistry
• 1,3-dipolar cycloadditions
• API synthesis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We gratefully acknowledge financial support from Spanish Ministry of Science and Innovation [grant number RTI2018-097662-B-I00], and Universidad Complutense de Madrid (Santander-UCM grant PR87/19-22691 and POP contract to JGC). We also acknowledge European Commission (the COST Action [grant number CA18112, Mechanochemistry for Sustainable Industry).