Continuous Flow Synthesis of α-Trifluoromethylthiolated Esters and Amides from Carboxylic Acids: a Telescoped Approach

A continuous flow approach to access alpha-trifluoromethylthiolated esters and amides using commercially available arylacetic acids and N-(trifluoromethylthio)phthalimide as the electrophilic reagent is described. The experimental protocol involves the in-flow conversion of the carboxylic acid into N-acylpyrazole followed by the alpha-trifluoromethylthiolation in a PTFE coil reactor and final reaction with primary or secondary amines, or alcohols, to afford in a telescoped process alpha-substituted SCF3 amides and esters, respectively, in good overall yield and short reaction times.