Semi-Industrial Fluorination of β-Keto Esters with SF₄: Safety vs Efficacy

The possibility of deoxofluorination of β-keto esters using SF₄ was investigated. The scope and limitation of the reaction were determined. The efficient method for the synthesis of β,β-difluorocarboxylic acids was elaborated based on the reaction. The set of mentioned acids, being the perspective building blocks for medicinal chemistry, were synthesized on multigram scale. The safety of SF₄ use was discussed. The described method does not improve upon the safety of using SF₄, but practical recommendations for working with the reagent are proposed. Despite the hazards of using toxic SF₄, a significant increase of efficacy in the synthesis of medicinal-chemistry-relevant building blocks, based on the reaction, in comparison with earlier described approaches is shown.