Selective Decarboxylative Fluorination of β-Keto Acids in Aqueous Media: 19F-NMR-Assisted Batch Optimization and Transfer to Continuous Flow
E. Cermjani,* C. Deckers, M. Maskos, T. H. Rehm*: Selective decarboxylative fluorination of β-keto acids in aqueous media: 19F-NMR-assisted batch optimization and transfer to continuous flow. Chem. Eur. J. 2025, 31, e202404435, DOI: 10.1002/chem.202404435
The synthesis of API relevant α-fluoro ketone phenacyl fluoride is finally described as a catalyst-free continuous flow process. This selective decarboxylative monofluorination is optimized in batch mode for aqueous and biocompatible conditions varying temperature, additives, and pH. Furthermore, benchtop NMR PAT was used for fundamental studies to a better understanding of the mechanism of the decarboxylative fluorination as well as the reaction pathways to α-difluorinated ketone derivatives.