Future medicinal chemists experience flow chemistry: optimization by experimental design of the limiting synthetic step to the antifungal drug econazole nitrate

Abstract

A practical experience to showcase the potential of flow technology in the synthesis optimization of drugs has been developed and carried out by fourth year undergraduate students in Pharmaceutical Chemistry and Technology (CTF) at the University of Perugia. In particular, we present an experiment aimed at optimizing the monobromination reaction of 2′,4′-dichloroacetophenone, the limiting step to the synthesis of the antifungal drug econazole nitrate. Throughout the experiment, the students learn how to integrate flow chemistry and experimental design to expedite experimental screening and reaction optimization. Moreover, the students have the possibility to exploit the use of automation to improve data generation and reduce human intervention in repetitive, expensive or hazardous experiments.