methyl 1H-indazole-3-carboxylate → HCID 10680335, compound

Participants

Reaction Steps

To a solution of indazole-3-carboxylic acid methyl ester (40.7 g, 231 mmol) in anhydrous tetrahydrofuran (700 mL) cooled in an ice bath was added slowly solid potassium tert-butoxide (28.3 g, 252 mmol). The mixture was stirred at the same temperature for 1 hr prior to the addition of 2-iododopropane (34.4 mL, 367 mmol). The final mixture was stirred for 12 h at ambient temperature, and refluxed for 12 h. After cooling to room temperature, the mixture was filtered, and the collected solid was rinsed with tetrahydrofuran (100 mL). The filtrates were combined, and concentrated to dryness under reduced pressure, affording crude 1-isopropyl-1H-indazole-3-carboxylic acid methyl ester (49.7 g) as a pale yellow oil. The crude material was purified by flash silica gel chromatography eluting with hexane/ethyl acetate (9/1 to 3/1) to yield 1-isopropyl-1H-indazole-3-carboxylic acid methyl ester (43 g, 197 mmol, >99% pure). 1H-NMR (CD3OD, 300 MHz): δ (ppm) 8.1-8.0 (1H, d), 7.6 (1H, d), 7.4 (1H, t), 7.2 (1H, t), 5.0 (1H, quin), 3.9 (s, 3H), 1.5 (6H, d).

Provenance & Evidence