反应详情

A mixture of ethyl 3,5-difluorobenzoylacetate (1.87 g, 8.19 mmol) and hydroxylamine hydrochloride (626 mg, 9.01 mmol) in acetic acid (24 ml) is stirred at reflux for 1 hr. The crude reaction mixture is concentrated in vacuo and azeotroped with toluene twice. The crude material is suspended in phosphorus oxychloride (37 ml) and triethyl amine (2.37 ml, 17.1 mmol) is added slowly. The reaction mixture is stirred at reflux for 2 days, concentrated in vacuo and azeothroped with toluene 3 times. The residue is dissolved in dichloromethane and passed on a plug of silica gel (elution with dichloromethane. After concentration in vacuo, the crude material is purified by flash chromatography (silica gel, dry loading, 5% diethyl ether in hexane) to give 3-(3,5-difluorophenyl)-5-chloroisoxazole (600 mg, 35%) as an off-white solid.

1. temperatureat reflux for 1 hr
2. customThe crude reaction mixture
3. concentrationis concentrated in vacuo
4. customazeotroped with toluene twice
5. stirringThe reaction mixture is stirred
6. temperatureat reflux for 2 days
7. concentrationconcentrated in vacuo and azeothroped with toluene 3 times
8. dissolutionThe residue is dissolved in dichloromethane
9. washelution with dichloromethane
10. concentrationAfter concentration in vacuo
11. customthe crude material is purified by flash chromatography (silica gel, dry loading, 5% diethyl ether in hexane)