Making Ibuprofen In Three Minutes

In less time than it takes most people to check out at a drugstore, David R. Snead and Timothy F. Jamison can whip up the popular nonsteroidal anti-inflammatory drug ibuprofen. The MIT chemists report that by using continuous-flow processing, they are able to synthesize the compound in three minutes from basic building blocks (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201409093). The synthesis demonstrates that continuous-flow procedures can handle extreme conditions and produce large quantities of active pharmaceutical ingredients without using massive reactors. In fact, the synthesis makes use of a harsh Friedel-Crafts acylation, employs the aggressive oxidant iodine monochloride, and the whole thing takes place in a reactor that’s about half the size of a standard lab fume hood. The five-stage process, which includes three bond-forming steps, one workup, and one liquid-liquid separation, produces about 8 g of ibuprofen in an hour. Snead and Jamison write that they were inspired by a 2009 continuous-flow ibuprofen synthesis from D. Tyler McQuade’s group at Florida State University. McQuade tells C&EN that the MIT effort shows that continuous-flow synthesis is “the future of chemical processing.”