The synthesis of bupropion hydrochloride under greener and safer conditions utilizing flow technologies

Abstract

Globally, major depressive disorders are a leading cause of disconsolateness affecting more than 300 million individuals. Bupropion is a unique dopamine-norepinephrine reuptake inhibitor (DNRI) commonly utilized in the treatment of depression, smoking cessation, ADHD and other addictions. Herein, we report our attempts to develop a greener, safer and more sustainable process for the preparation of bupropion hydrochloride employing flow chemistry. The use of obnoxious and corrosive liquid bromine was evaded through the employment of polymer-bound pyridinium tribromide and environmentally questionable solvents NMP and DMF were substituted with greener co-solvent systems with appreciable success. The final telescoped flow process afforded bupropion hydrochloride in a 69% overall yield, with improved process mass intensity, productivity and purity, as well as a reduction in reagents/solvents designated as red or amber in terms of H-codes.