Reconfiguration of a Continuous Flow Platform for Extended Operation: Application to a Cryogenic Fluorine-Directed ortho-Lithiation Reaction

A flow platform for preparing various aromatic scaffolds using a low-temperature fluorine-directed ortho -lithiation reaction has been successfully reconfigured to allow large-scale processing over extended reaction periods. During the course of this work several key factors have resulted in the development of new technology such as stainless steel y-piece fittings capable of hosting a thermocouple at the point of mixing which directly controls the power output of a cryogenic cooling device. These developments have enabled the continuous processing of an industrially relevant product, where adequate mixing, cooling, and exotherm control are important for successful operation. The configuration culminates in a large-scale campaign where the flow platform is utilised to process over 100 g of pure product over 7 h, in a yield of 80% after workup.