Triethylamine → (3-Phenyl-5-(trifluoromethyl)isoxazol-4-yl)methanol

Temperature

-10 °C

To a solution of 3-phenyl-5-trifluoromethyl-isoxazole-4-carboxylic acid (5.0 g, 19 mmol in THF (60 mL) at −10° C. was added triethylamine (2.0 g, 2.71 mL, 19 mmol) and then a solution of ethylchloroformate (2.1 g, 1.9 mL, 19 mmol) in THF (10 mL) added keeping the temperature below −5° C. After 30 min the mixture was filtered and the filtrate cooled to −10° C. and a suspension of sodiumborohydride (1.8 g, 49 mmol) in water (20 mL) added over 15 minutes keeping the temperature below −5° C. The mixture was then allowed to warm up to room temperature overnight and diluted with HCl (1 N) and extracted with ethyl acetate. The combined organic layers were then washed with water and brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1) afforded the title compound (3.1 g, 66%) as a white solid. MS: m/e=243.1 [M]

1. customthe temperature below −5° C
2. filtrationAfter 30 min the mixture was filtered
3. additionadded over 15 minutes
4. customthe temperature below −5° C
5. temperatureto warm up to room temperature overnight
6. extractionextracted with ethyl acetate
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=100:0 to 1:1)

ORD record

ord-9a3521a825b0430baa75c9549cb823d7

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846719B2