Continuous Process for Production of CuCF3 via Direct Cupration of Fluoroform

The first continuous flow process has been developed for the synthesis of a superior trifluoromethylating reagent, ligandless CuCF3, from fluoroform, by far the best CF3 source in terms of availability, cost, and atom economy. Optimization of the residence time and feed rates for CHF3 (gas), the cuprating reagent (premade from Cu Cl and t-BuOK in a 1:2 ratio) in DMF, and the stabilizer (Et3N.3HF) at 23 degrees C and atmospheric pressure has allowed for the continuous production of CuCF3 in consistently high yields of up to 94%. The thus produced CuCF3 has been shown to be as highly efficient a trifluoromethylating agent as the one from the previously developed batch process.