3,5-bis(trifluoromethyl)-acetophenone could be produced through the following synthetic routes.

A 100-mL, three-necked, round-bottom flask equipped with a teflon-coated thermocouple probe, inert gas inlet, a 100-mL pressure-equalizing addition funnel fitted with a rubber septum, and a magnetic stirbar is charged with 3,5-bis(trifluoromethyl)bromobenzene (20.0 g, 11.8 mL, 68.3 mmol) and 35 mL of anhydrous THF. The solution is cooled to -5 °C in a ice-salt water bath and a solution of i-PrMgCl in THF (37.6 mL, 2 M, 75.2 mmol) is added dropwise over 1 hr at a rate such that the internal reaction temperature does not exceed 0°C. Upon completion of the addition, the reaction mixture is stirred for 1 hr at 0 to -10 °C.

A 250-mL, three-necked, round-bottomed flask equipped with a teflon-coated magnetic stir bar, a reflux condenser fitted with an inert gas inlet, a glass stopper, and a septum pierced by a teflon-coated thermocouple probe is charged with acetic anhydride (24.4 mL, 258 mmol) and then cooled to -5 °C in a ice-salt water bath. The solution of 3,5-bis(trifluoromethyl)phenylmagnesium chloride (at -5 °C, prepared as described above) is transferred into the flask containing acetic anhydride via an 18-gauge, 2-ft, double-ended needle at a rate such that the internal reaction temperature does not exceed 0 °C (ca. 2 hr). The resulting pale yellow solution is stirred for 30 min at 0 °C. The flask is removed from the ice-water bath and 35 mL of deionized water is added dropwise over 1 hr. The resulting biphasic mixture is heated at 60 °C in an oil bath for 15 min. The reaction mixture is then allowed to cool to room temperature. The organic layer is separated and diluted with 35 mL of MTBE. The resulting solution is transferred to a 250-mL Erlenmeyer flask and vigorously stirred at 15 °C while 2 mL of aqueous 2.5 N NaOH is added dropwise so that the pH of the aqueous phase reaches 7.1. The organic phase is separated and washed with two 20-mL portions of saturated aqueous NaHCO₃ solution and 20 mL of brine, dried over Na2SO4, and concentrated by rotary evaporation (20 mmHg) at room temperature. The residue is transferred to a 50-mL, one-necked, pear-shaped flask. Purification by bulb-to-bulb distillation at 25 mmHg (distillate collected at 122-132 °C) affords 15.1-15.2 g (86-87%) of 3,5-bis(trifluoromethyl)-acetophenone as a clear, colorless oil.