Selective Decarboxylative Fluorination of β-Keto Acids in Aqueous Media: 19F-NMR-Assisted Batch Optimization and Transfer to Continuous Flow

The selective decarboxylative fluorination of 3-oxo-3-phenylpropionic acid is used as a benchmark reaction to optimize it under biocompatible conditions in batch and to transfer it to continuous flow mode. The reaction conditions are varied with respect to temperature, fluorinating reagents, inorganic base additives, and pH, as these parameters have been identified as having a significant impact on the process. The formation of the products and any by-products is analyzed using gas chromatography (GC) and 19F nuclear magnetic resonance spectroscopy (NMR). Once optimal conditions have been determined, the reaction is carried out using an automated continuous laboratory synthesis system that features a mesostructured capillary reactor and an integrated 19F-NMR spectrometer for real-time monitoring of the reaction. The work presented here represents the initial phase of a multi-step continuous flow process that will include additional biocatalyzed downstream reactions in future applications.