Acetic Anhydride → 1H-indazol-4-ol

Participants

Reaction Steps

Acetic anhydride (16.4 ml, 174 mmol), tetrabutylammonium bromide (933 mg, 2.90 mmol), potassium acetate (11.4 g, 116 mmol) and isoamyl nitrite (11.7 ml, 86.9 mmol) were added to a solution of 3-(acetylamino)-2-methylphenyl acetate (12.0 g, 57.9 mmol) in ethyl acetate (120 ml) at room temperature, and the resulting mixture was refluxed for 7 hours. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1). Subsequently, the residue purified was dissolved in methanol (50 ml) and a 2N-aqueous sodium hydroxide solution (47.9 ml) was added thereto at room temperature and stirred for 1 hour. The methanol was distilled off under reduced pressure, and the resulting aqueous solution was adjusted to pH 4 to 5 by dropwise addition of hydrochloric acid and then extracted with acetic acid. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=2/1) to obtain 1H-indazol-4-ol (3.62 g, 47%).

Provenance & Evidence