154057-13-3

1514-87-0

5326-34-1

154057-13-3

Step A: Synthesis of 2-nitro-4-methylbenzotrifluoride In a dry reaction flask, 6.00 g (27.8 mmol) of 4-bromo-3-nitrotoluene, 5.86 mL (8.03 g, 55.6 mmol) of methyl chlorodifluoroacetate and 1.93 g (33.4 mmol) of potassium fluoride were added. Subsequently, 5.31 g (27.8 mmol) of cuprous iodide and 25 mL of anhydrous DMF were added and the reaction mixture was stirred at 110 °C for 2 days. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with aqueous citric acid and extracted with ethyl acetate 3 times. The organic phases were combined, washed sequentially with water and saturated saline, and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated and the resulting residue was purified by rapid column chromatography on silica gel (eluent ratios of 100:1 and 25:1 hexane-ethyl acetate) to give 3.25 g (57% yield) of 4-methyl-2-nitrotrifluoromethylbenzene as a yellow liquid. The product showed a single spot by TLC (unfolding agent 4:1 hexane-ethyl acetate). Mass spectrum (EI) m/e 205 (M+). 400 MHz 1H NMR (CDCl3) δ 2.48 (s, 3H), 7.49 (d, J = 8 Hz, 1H), 7.67 (s, 1H) overlapping with 7.68 (d, J = 8 Hz, 1H) signal.