The general procedure for the synthesis of 6-(trifluoromethyl)-1H-indazole using 2-fluoro-4-(trifluoromethyl)benzaldehyde as starting material was as follows: to a stirring solution of 2-fluoro-4-(trifluoromethyl)benzaldehyde (200 mg, 1.04 mmol, 1.0 eq.) in THF (5 mL) at room temperature was added NH2OMe (174 mg, 2.08 mmol 2.0 eq.). The reaction mixture was stirred at room temperature for 3 h. After stirring, (NH2)2-H2O (67 mg, 2.08 mmol, 2.0 eq.) was added, followed by refluxing the mixture for 3 h. The reaction was completed with a solution of saturated NH2OMe (5 mL). Upon completion of the reaction, the reaction was quenched with saturated aqueous Na2S2O3 and extracted with EtOAc. The organic phase was dried over MgSO4 and concentrated under reduced pressure to give the crude product. The crude product was purified by Yamazen automated chromatography using Hex:EtOAc = 9:1 as eluent to yield 6-(trifluoromethyl)-1H-indazole (121 mg, 37% yield) as a colorless solid. The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3) and MS (ESI): 1H NMR δ 10.57 (1H, br s), 8.18 (1H, s), 7.89 (1H, dd, J = 9.0,0.5 Hz), 7.42 (1H, dd, J = 9.0,3.0 Hz); MS (ESI) m/z 203 [(M + Na)+], retention time 1.00 min (condition A).
