(2‐Ethylhexyl)sodium: A Hexane‐Soluble Reagent for Br/Na‐Exchanges and Directed Metalations in Continuous Flow

We report the on‐demand generation of hexane‐soluble (2‐ethylhexyl)sodium (1) from 3‐(chloromethyl)heptane (2) using a sodium‐packed‐bed reactor under continuous flow conditions. Thus, the resulting solution of 1 is free of elemental sodium and therefore suited for a range of synthetic applications. This new procedure avoids the storage of an alkylsodium and limits the handling of metallic sodium to a minimum. (2‐Ethylhexyl)sodium (1) proved to be a very useful reagent and undergoes in‐line Br/Na‐exchanges as well as directed sodiations. The resulting arylsodium intermediates are subsequently trapped in batch with various electrophiles such as ketones, aldehydes, Weinreb‐amides, imines, allyl bromides, disulfides and alkyl iodides. A reaction scale‐up of the Br/Na‐exchange using an in‐line electrophile quench was also reported.