ethyl 3-(3,5-difluorophenyl)-3-oxopropanoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Methylpyrazol-5-amine (526 mg) and ethyl 3-(3,5-difluorophenyl)-3-oxopropanoate (879 g) are stirred overnight in a pyridine (30 mL) solvent at 85° C. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The extracted organic layer is washed with brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure and purified by column chromatography to yield the target compound (521 mg). the reaction solvent is removed by distillation under reduced pressure The remainder is extracted with ethyl acetate and water The extracted organic layer is washed with brine The dehydrated organic layer is distilled under reduced pressure purified by column chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. at reflux for 1 hr The crude reaction mixture is concentrated in vacuo azeotroped with toluene twice 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 elution with dichloromethane After concentration in vacuo the crude material is purified by flash chromatography (silica gel, dry loading, 5% diethyl ether in hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Methylpyrazol-5-amine (526 mg) and ethyl 3-(3,5-difluorophenyl)-3-oxopropanoate (879 g) are stirred overnight in a pyridine (30 mL) solvent at 85° C. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The extracted organic layer is washed with brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure and purified by column chromatography to yield the target compound (521 mg). the reaction solvent is removed by distillation under reduced pressure The remainder is extracted with ethyl acetate and water The extracted organic layer is washed with brine The dehydrated organic layer is distilled under reduced pressure purified by column chromatography