Batch–flow hybrid synthesis of the antipsychotic clozapine

Abstract

The development of batch–flow hybrid processes is becoming an attractive prospect through which chemists can make use of the best aspects of both technologies. We have reported the implementation of an on-the-fly purification by trituration which can also be utilised to perform solvent swaps. We have demonstrated this concept through the synthesis of the antipsychotic clozapine. In addition, we report a novel means of performing a reduction of an aryl nitro group under flow conditions and an overall improved process route for the total synthesis of clozapine.