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

Temperature

0 °C

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).

1. customto precipitate
2. stirringThe solution was stirred at 0° C. for approximately 30 minutes
3. temperatureto warm to ambient temperature
4. concentrationThe solution was concentrated
5. additionwater was added
6. extractionThe solution was extracted twice with ethyl acetate
7. washThe combined organic layers were washed with brine
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated
10. custompurified by chromatography (silica gel, 0-40% ethyl acetate in hexanes gradient elution)

ORD record

ord-f4b4387d7d6d46aabba3b184adbecc0c

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07960552B2