Acetic Anhydride → HCID 22933528, compound

Participants

Reaction Conditions

Reaction Steps

Acetic anhydride (377 μl, 4.00 mmol) was added dropwise to a solution of 4-methoxy-2-methyl-3-(trifluoromethyl)aniline (513 mg, 2.50 mmol) in ethyl acetate (3.0 ml) at room temperature. Ethyl acetate (4.5 ml) was added to the solidified reaction solution and the resulting mixture was slowly heated to 65° C. and stirred for 15 minutes while maintaining the temperature. The resulting reaction solution was cooled to room temperature, followed by adding thereto acetic anhydride (708 μl, 7.50 mmol), tetrabutylammonium bromide (40.3 mg, 0.125 mmol), potassium acetate (491 mg, 5.00 mmol) and isopentyl nitrite (437 μl, 3.25 mmol) in that order at room temperature. The resulting mixture was slowly heated to 65° C. and stirred for 6 hours while maintaining the temperature. After cooling, the mixture was partitioned and extracted with water and ethyl acetate, and the organic layer was washed with a 5% aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure to obtain a crude product (800 mg). The crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 to 6/1) to obtain 1-acetyl-5-methoxy-4-(trifluoromethyl)-1H-indazole (496 mg, 77%).

Provenance & Evidence