Isopropyl chloroformate → [5-Cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol

Temperature

0 °C

To a solution of 5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylic acid (808 mg, 2.59 mmol) in THF (13 mL) at 0° C. was added triethylamine (0.361 mL, 2.59 mmol) followed by isopropyl chloroformate (1 M in toluene, 2.59 mL, 2.59 mmol). The solution was stirred at 0° C. for approximately 1 hour and then was filtered into a solution of sodium borohydride (127 mg, 3.37 mmol) in water (1 mL) at 0° C. The solution was allowed to warm to ambient temperature and was then concentrated. Water was added and the mixture was extracted three times 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-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol (478 mg, 62%). 1H-NMR (400 MHz, DMSO-d6) δ 8.79 (s, 2H), 4.97-4.94 (m, 1H), 4.16-4.15 (m, 2H), 3.92-3.83 (m, 1H), 2.40-2.30 (m, 4H), 2.10-2.01 (m, 1H), 1.99-1.89 (m, 1H).

1. temperatureto warm to ambient temperature
2. concentrationwas then concentrated
3. additionWater was added
4. extractionthe mixture was extracted three times with ethyl acetate
5. washThe combined organic layers were washed with brine
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated
8. custompurified by chromatography (silica gel, 0-40% ethyl acetate in hexanes gradient elution)

ORD record

ord-71db0fd2262d4cc5af51692801385486

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07960552B2