2-Methyl-4-methoxyaniline → 5-Methoxy-1H-indazole

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Reaction Conditions

Reaction Steps

A solution of 4-methoxy-2-methylaniline (2 ml) in dichloromethane (10 ml) was treated with triethylamine (3.27 ml). The mixture was cooled to 0° C. then treated with acetic anhydride (2.38 ml), then stirred at ambient temperature for 1 hour, then cooled to 0° C. when a pink solid precipitated. This solid was filtered, then washed with cold dichloromethane and then dissolved in acetic acid (55 ml) and concentrated hydrochloric acid (20 ml). This solution was cooled to −5° C., then treated with a solution of sodium nitrite (2.68 g) in water (20 ml), then stirred at that temperature for 1 hour and then treated with water (100 ml). This mixture was stirred vigorously at 0° C. for 10 minutes after which a yellow solid precipitated. This solid was filtered, then washed with water and then dissolved in toluene (13 ml). This solution was heated to 80° C. for 1.5 hours, then cooled and then washed with aqueous 1N sodium carbonate solution. The organic phase was extracted three times with aqueous 2N hydrochloric acid and the acid extracts chilled and then made alkaline by addition of aqueous 5N sodium hydroxide solution. The aqueous layers were extracted three times with ethyl acetate and the combined organic layers were dried over magnesium sulfate and then evaporated to yield 5-methoxy-1H-indazole (0.410 g) as a yellow solid. LC-MS (METHOD B): RT=1.32 minutes; 149 (M+H)+.

Provenance & Evidence