Aqueous Base Promoted O -Difluoromethylation of Carboxylic Acids with TMSCF 2 Br: Bench-Top Access to Difluoromethyl Esters

A method for the -difluoromethylation of carboxylic acids using commercially available TMSCF Br is disclosed. The devised benchtop reaction system is air-stable and offers mild reaction conditions while using readily available reagents and solvents. The method is applicable to both aliphatic and aromatic carboxylic acids while demonstrating compatibility with a range of commonly encountered functional groups. The difluoromethyl esters of FDA approved drugs and pharmaceutically relevant molecules are also presented, demonstrating the potential for late-stage functionalization.