Control of Hydrogen Fluoride Formation and Release during a Large-Scale Nitroarene Reduction in the Manufacture of AZD9977

Abstract

A nitroarene reduction process was developed to run on a multi-kilo scale with optimized conditions to reduce the formation of hydrogen fluoride through catalytic hydrodefluorination and an unanticipated oxidative pathway. Process understanding and optimization, including the characterization of the kinetics of the hydrogenation, are disclosed as well as an innovative way of neutralizing any hydrogen fluoride formed on plant scale without the need to purge the vessel with inert gas.