Hydrochloric Acid → Ethyl 3-(4-chloro-3-methylphenyl)-3-oxopropanoate

Temperature

80 °C

A mixture of 4′-chloro-3′-methylacetophenone (10.0 g), sodium hydride (60%, oil, 2.38 g) and diethyl carbonate (80 ml) was stirred for 90 min at 80° C. 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-(4-chloro-3-methylphenyl)-3-oxopropionate 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 (10.6 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 (8.24 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, and crystals of ethyl 5-(4-chloro-3-methylphenyl)isoxazole-4-carboxylate (9.26 g, yield 59%) were obtained from a fraction eluted with ethyl acetate-hexane (1:5, volume ratio) and recrystallized from hexane to give a colorless prism. melting point: 50–51° C.

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

ORD record

ord-2ff89f8c631143688986030ff8020c73

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07022725B2