Hydrochloric Acid → 5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole-6-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

6-Bromo-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole (1.64 g, 4.11 mmol) was dissolved in 9:1 methanol/water degassed with carbon monoxide (27 mL). To this was added 1-((3-(diphenylphosphino)propyl)(phenyl)phosphino)benzene (85 mg, 0.21 mmol), palladium (II) acetate (46 mg, 0.21 mmol), and potassium carbonate (1.70 g, 12.3 mmol). The reaction mixture was heated to 60° C. for 20 hours. The reaction mixture was then acidified to pH 1 by the addition of 5M hydrochloric acid, and the crude reaction mixture was partitioned between ether and water. The aqueous layer was extracted with ether, and the combined organic layers were washed with brine. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified on a silica gel column, eluting with a gradient of 0.2-10% methanol/dichloromethane to yield 5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole-6-carboxylic acid (7a) (724 mg, 48%).

Provenance & Evidence