Greening the Valsartan Synthesis: Scale-up of Key Suzuki-Miyaura Coupling over Silia Cat DPP-Pd

The study of the scale-up of the heterogeneous Suzuki-Miyaura coupling reaction in batch conditions between 2-chlorobenzonitrile and 4-tolylboronic acid, a key step in valsartan synthesis, to produce 4?-methyl-2- biphenylcarbonitrile over the SiliaCat DPP-Pd catalyst in ethanol under reflux allows to identify the optimal reaction conditions. The catalyst, regardless of limited Pd leaching, is not reusable, and the method can be effectively applied to the high yield synthesis of several coupling products, opening the route to efficient continuous coupling syntheses.