反应详情

温度

-10 °C

To a solution of 3-(4-fluoro-phenyl)-isoxazole-4-carboxylic acid (40 g, 193 mmol) in THF (400 mL) at −10° C. was added triethylamine (27.1 mL, 193 mmol) and then a solution of ethylchloroformate (18.8 mL, 193 mmol) in THF (120 mL) added keeping the temperature below −5° C. After 1 h the mixture was filtered and the filtrate cooled to −10° C. and a suspension of sodiumborohydride (19 g, 483 mmol) in water (120 mL) added over 15 minutes keeping the temperature below −5° C. The mixture was then allowed to warm up to room temperature over 2 h and diluted with aqueous sodium hydroxide (1 N, 700 mL) and extracted with tert-butylmethylether. The combined organic layers were then washed with water and brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=1:1) afforded the title product (20.1 g, 54%) which was obtained as white solid. MS: m/e=194.1 [M+H]+.

1. customthe temperature below −5° C
2. filtrationAfter 1 h the mixture was filtered
3. additionadded over 15 minutes
4. customthe temperature below −5° C
5. temperatureto warm up to room temperature over 2 h
6. extractionextracted with tert-butylmethylether
7. washThe combined organic layers were then washed with water and brine
8. dry with materialdried over sodium sulfate
9. customevaporated
10. customPurification by chromatography (SiO2, heptane:ethyl acetate=1:1)