Hydrazine → 4,6-Difluoro-1H-indazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,4,6-trifluorobenzaldehyde (0.80 g, 5.0 mmol) in 1,2-dimethoxyethane (10 mL) were added potassium carbonate (1.04 g, 7.5 mmol) and O-methylhydroxylamine hydrochloride (438 mg, 5.25 mmol). The reaction mixture was heated at 50° C. for 5 h then cooled to room temperature and filtered, rinsing with dichloromethane. The filtrate was concentrated. The residue was dissolved in 1,2-dimethoxyethane (10 mL) and hydrazine (0.17 mL, 5.5 mmol) was added. The reaction mixture was heated at 100° C. for 1.5 h. Additional hydrazine (0.17 mL, 5.5 mmol) was added and heating was continued for 30 min. Thereaction was cooled to room temperature, poured into water, and extracted with ethyl acetate. The organic layer was washed with sat LiCl and brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 20% to 50% EtOAc/heptane to provide 358 mg (47%) of 4,6-difluoro-1H-indazole as a light yellow solid. 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 13.47 (br. s., 1H), 8.19 (s, 1H), 7.22 (d, J=9.1 Hz, 1H), 6.96 (td, J=10.0, 1.9 Hz, 1H).

Provenance & Evidence