AC oncise Flo wS ynthesis of Efavirenz

Efavirenz is an essential medicine for the treatment of HIV ,w hich is still inaccessible to millions of people worldwide .A novel, semi-continuous process provides rac- Efavirenz with an overall yield of 45 %. This streamlined proof-of-principle synthesis relies on the efficient copper- catalyze df ormation of an aryl isocyanate and as ubsequent intramolecular cyclization to install the carbamate core of Efavirenz in one step .T he three-step method represents the shortest synthesis of this life-saving drug to date. For the developing world, the affordability of critical medicines still remains the greatest obstacle to therapy. (1) While competition from generic manufacturers has led to ad ecrease in prices ,v irtually all active pharmaceutical ingredients (APIs) are still produced by multiple distinct chemical transformations in batch reactors .O ver the past decade ,c ontinuous processes have emerged as an effective means to conduct chemical syntheses ,a st hey offer increased control over the reaction conditions .I mproved product quality and safety are accompanied by ar educed environ- mental impact compared to traditional batch syntheses. (2, 3) Accordingly ,p roduction costs can be significantly lowered through flow-enabled, improved manufacturing. (4) Efforts to streamline API syntheses have led to several linear (5 ,6 ) and divergent (7) continuous processes to meet the rising global demand for medicines. An efficient synthesis of Efavirenz, ad rug that is still inaccessible to millions of people worldwide ,h olds great potential both scientifically and socially. (8) This potent non- nucleoside reverse transcriptase inhibitor (NNRTI) is one of the preferred agents used in combination therapy for first-line treatment of the human immunodeficienc yv irus (HIV). (9) We sought to develop ac oncise ,a tom-economic ,a nd continuous synthetic route that avoids the toxic or expensive reagents