[Synthesis]
To 4-(trifluoromethyl)toluene (22b, 9.0 g, 56 mmol), 20 ml of trifluoroacetic acid (TFA) and 5.6 ml of 28% sulfuric acid (H2SO4) were added to a round bottom flask. N-bromosuccinimide (NBS, 10.0 g, 56 mmol, 1 equiv) was added to the reaction mixture in batches. The reaction was stirred overnight at room temperature.After 20 h, post-treatment was performed: the reaction mixture was poured into 100 ml of ice water and the organic layer (oily residue) was separated from the aqueous layer by extraction with ether (Et2O). The ether layers were combined, dried with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to remove the solvent. The pure product 3-bromo-4-methylbenzotrifluoride (7.86 g, yield 59%) was obtained as a light yellow oil. Structural confirmation: The product was analyzed by RP-HPLC under the following conditions: HP 1100 HPLC system, Waters 3.9×150 mm NovaPak HR C18 guard column, injection volume of 0.010 mL, flow rate of 1.5 mL/min, injection loop of 1.500 mL, detection wavelength of 254 nm, mobile phase A was water (containing 0.1% v/v TFA). Mobile phase B was acetonitrile (containing 0.1% v/v TFA), gradient program: initial 10% B held for 1 min, linear increase to 80% B in 1-10 min, linear increase to 100% B in 10-11 min, held for 1 min. Product retention time was 11.7 min.1H NMR (400 MHz, CDCl3): δ 2.45 (s, 3H), 7.34 (d, J=8.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.80 (s, 1H). |