Continuous flow synthesis and crystallization of modafinil: a novel approach for integrated manufacturing†

Abstract

This study reports efforts toward the integrated advanced manufacturing of the anti-narcoleptic drug modafinil. It showcases a holistic approach from flow synthesis to purification via continuous crystallization. The integration strategy included a necessary optimization of the reported flow synthesis for modafinil, enabling prolonged operation and consistent crude quality. The reactor effluents were subsequently processed downstream for purification utilizing two single stage mixed suspension mixed product removal crystallizers. The first stage was an antisolvent cooling crystallization, providing refined modafinil with >98% yield. The second cooling crystallization delivered crystalline modafinil with >99% purity in the required polymorphic form I suitable for formulation.