Hydrochloric Acid → Ethyl 3-oxo-3-(4-(trifluoromethyl)phenyl)propanoate

Temperatur

80 °C

A mixture of 4′-trifluoromethylacetophenone (10.0 g), sodium hydride (60%, oil, 2.13 g) and diethyl carbonate (80 ml) was stirred at 80° C. for 90 min. Water was added to the reaction mixture, and the mixture was neutralized with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-oxo-3-(4-trifluoromethylphenyl)propionate was obtained as an oil from a fraction eluted with ethyl acetate-hexane (1:9, volume ratio). A mixture of this oil and N,N-dimethylformamide dimethylacetal (9.50 g) was refluxed for 1 hr. The reaction mixture was concentrated, and the residue was dissolved in ethanol (80 ml). To the obtained solution was added hydroxylamine hydrochloride (7.39 g), and the mixture was refluxed for 2 hr. The reaction mixture was concentrated, water was added to the residue and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, the crystals obtained from a fraction eluted with ethyl acetate-hexane (1:9, volume ratio) were recrystallized from hexane to give ethyl 5-(4-trifluoromethylphenyl)isoxazole-4-carboxylate (8.42 g, yield 56%) as a colorless prism. melting point: 53–54° C.

1. extractionextracted with ethyl acetate
2. washThe ethyl acetate layer was washed with saturated brine
3. dry with materialdried (MgSO4)
4. concentrationconcentrated

ORD-Eintrag

ord-f2ebaaef382b4b08a0712b16f7bb431f

Quelldatensatz

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07022725B2