Scalable electrocatalyzed formation of C–O bonds using flow reactor technology†

Abstract

The development of modular and robust synthetic routes that can serve both in medicinal and process chemistry settings is rare. Generally, highly modular medicinal chemistry routes are too hazardous and expensive to be translated into a process chemistry environment. Taking the case study of delamanid, a pharmaceutical compound used for multidrug-resistant tuberculosis treatment, the development of a sustainable and modular but scalable formation of C–O bonds via an electrocatalytic method is presented. In this work, the electrochemical batch reaction was studied, addressing critical reproducibility issues related with the process. Furthermore, the reaction was successfully translated to a flow electrochemical reactor design, which allowed the use of carbon felt electrodes. The high modularity of the protocol was demonstrated by the synthesis of 11 different examples, while the scalability of the reaction was proven by a gram scale preparation of a key intermediate for the synthesis of delamanid.