Isopropyl chloroformate → 5-Cyclopropyl-3-(3,5-dichloro-4-pyridyl)isoxazole-4-methanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylic acid (155 mg, 0.52 mmol) and triethylamine (0.072 mL, 0.52 mmol) in tetrahydrofuran (3 mL) at 0° C. was added isopropyl chloroformate (0.52 mL, 0.52 mmol). A white solid was seen to precipitate. The mixture was stirred at 0° C. for approximately 1 hour and then filtered into a stirring solution of sodium borohydride (25 mg, 0.67 mmol) in water at 0° C. The solution was stirred at 0° C. for approximately 30 minutes and the allowed to warm to ambient temperature. The solution was concentrated and water was added. The solution was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, concentrated and purified by chromatography (silica gel, 0-40% ethyl acetate in hexanes gradient elution) to afford [5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol (83 mg, 56%). 1H-NMR (400 MHz, CDCl3) δ 8.62 (s, 2H), 4.44 (s, 2H), 2.20-2.14 (m, 1H), 1.30-1.44 (m, 4H).

Provenance & Evidence