116965-16-3

154057-13-3

107-06-2

116965-16-3

Step B Synthesis of 3-nitro-4-(trifluoromethyl)benzoic acid: To a rapidly stirred mixture containing 1.00 g (4.88 mmol) of 2-nitro-4-methylbenzotrifluoride (from Step A), 236 mg (0.732 mmol) of tetra-n-butylammonium bromide, 51 mg (0.244 mmol) of ruthenium trichloride hydrate, and 2 mL of 1,2-dichloroethane to which 5.8 mL (~22 mmol) of 13% aqueous sodium hypochlorite solution (~3.8 M) was added in five additions. At each addition of sodium hypochlorite solution, the pH of the reaction mixture was adjusted by the addition of 5N NaOH solution and maintained between 8.5 and 10.5. The next portion of sodium hypochlorite solution was added only after the pH had stabilized for about 5 minutes. The entire addition process took about 2 h. The final pH was 10.3. The reaction mixture was stirred overnight at 45 °C and then cooled to room temperature for two-phase separation. The aqueous phase was acidified to pH 3 with 20% sulfuric acid and subsequently extracted three times with ethyl acetate. The combined organic extracts were washed sequentially with water (3 times) and brine and then dried with anhydrous Na2SO4. The residue obtained by concentrating the organic phase was dissolved in 5% NaHCO3 aqueous solution and adjusted with 5% NaOH to pH 9. The aqueous phase was washed sequentially with dichloromethane (2 times) and ether. Subsequently, the aqueous phase was acidified to pH 3 with 20% sulfuric acid and extracted with ethyl acetate to afford 563 mg (49% yield) of the title compound as an off-white solid with a melting point of 156-158° C. TLC analytical conditions: 1:1 hexanes-EtOAc; Mass Spectrometry (EI) m/e 235 (M+); 200 MHz 1H NMR (CD3OD) δ 7.87 (d, J= 8Hz, 1H), 8.31 (d, J=8Hz, 1H), 8.45 (s, 1H).