Hydrochloric Acid → Ethyl 3-(5-chlorothiophen-2-yl)-3-oxopropanoate

Temperature

80 °C

A mixture of 2-acetyl-5-chlorothiophene (10.0 g), sodium hydride (60%, oil, 2.49 g) and diethyl carbonate (80 ml) was stirred at 80° C. for 30 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-(5-chloro-2-thienyl)-3-oxopropionate was obtained as an oil from a fraction eluted with ethyl acetate-hexane (1:5, volume ratio). A mixture of this oil and N,N-dimethylformamide dimethylacetal (11.1 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 (8.65 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 the crystals obtained from a fraction eluted with ethyl acetate-hexane (1:5, volume ratio) were recrystallized from ethyl acetate-hexane to give ethyl 5-(5-chloro-2-thienyl)isoxazole-4-carboxylate (9.34 g, yield 58%) as a colorless prism. melting point: 74–75° 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-98c87d7d45644f8d95d644d54f04a969

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07022725B2