Micellar Reaction System Proven On Kilogram Scale

Process chemists at Novartis have demonstrated that an aqueous reaction system for carrying out organic reactions such as Suzuki-Miyaura cross-couplings is robust enough for a multistep, kilogram-scale synthesis of one of the company’s active pharmaceutical ingredients that is under development. Compared with the same synthesis using organic solvents, the aqueous processes operate under milder conditions and improve selectivity and product yield while reducing solvent use, water use, amount of palladium catalyst, synthesis time, and overall cost by up to 30%, according to Fabrice Gallou and coworkers, who evaluated the technology (Green Chem. 2015, DOI: 10.1039/c5gc02371h). The chemistry is based on a designer surfactant, called TPGS-750-M, invented by Bruce H. Lipshutz and his group at the University of California, Santa Barbara. When added to water, the surfactant forms lipophilic nanomicelles. The size and structure of these tiny reaction vessels control the flux of reactants, catalyst, and product into and out of the nanomicelles to optimize reaction rates. The multistep kilogram process is “to the best of our knowledge a first in the pharmaceutical industry and constitutes a real milestone,” the Novartis chemists say.