3',5'-Bis(trifluoromethyl)acetophenone

68120-60-5

30071-93-3

General procedure for the synthesis of 3,5-bis(trifluoromethyl)acetophenone from (R)-1-[3,5-bis(trifluoromethyl)-phenyl]ethanol: BTC (0.41 g, 1.39 mmol) was dissolved in anhydrous dichloromethane (5 mL) under the protection of nitrogen and cooled to -15 °C in an ice-salt bath. At this temperature, a solution of (R)-1-[3,5-bis(trifluoromethyl)-phenyl]ethanol (1.24 g, 4.17 mmol) in anhydrous dichloromethane (5 mL) was slowly added dropwise for 0.5 hours. After continued stirring for 0.5 h, an anhydrous dichloromethane (5 mL) solution of benzyl alcohol (0.3 g, 2.78 mmol) was added dropwise for 0.5 h at the same temperature. After stirring for 0.5 h, triethylamine (0.84 g, 8.34 mmol) was slowly added while making sure that the reaction temperature was kept below -15 °C. Upon completion of the reaction, 10% aqueous hydrochloric acid was added dropwise under ice bath conditions until the pH of the reaction mixture reached 2. The organic layer was separated by extracting the mixture with hexane or petroleum ether (10 mL x 2). After concentration of the organic layer, it was purified by fast chromatography (silica gel; hexane) to afford the target product 3,5-bis(trifluoromethyl)acetophenone (0.27 g, 92% yield). The aqueous layer can be used to recover by-product V and excess (R)-1-[3,5-bis(trifluoromethyl)-phenyl]ethanol.