Hydrochloric Acid → 5-methoxy-4-methyl-1H-indazole

Participants

Reaction Steps

Acetic anhydride (1.46 ml, 15.52 mmol), tetrabutylammonium bromide (83 mg, 0.259 mmol), potassium acetate (1.02 g, 10.35 mmol) and isoamyl nitrite (0.904 ml, 6.73 mmol) were added to a solution of N-(4-methoxy-2,3-dimethylphenyl)acetamide (1.0 g, 5.175 mmol) in ethyl acetate (10 ml) at room temperature, and the resulting mixture was refluxed. After 6 hours, the ethyl acetate was distilled off with heating, and a 6M-aqueous sodium hydroxide solution (10.35 ml, 62.1 mmol) was added dropwise to the residue at 60° C. After 1 hour, the reaction solution was adjusted to pH 8 to 9 with a 3M-aqueous hydrochloric acid solution and extracted with chloroform (50 ml×2), and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain 5-methoxy-4-methyl-1H-indazole (456 mg, 54%).

Provenance & Evidence