反应详情

In a solution of 1.70 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl-N-(hydroxymethyl)benzoic acid amide in 20 mL of dichloromethane, 0.68 g of thionyl chloride was added at room temperature with stirring, and stirred at the same temperature for 2 hours. Then, the solvent was distilled off under reduced pressure, and the residue was dissolved in 10 mL of tetrahydrofuran. 1.50 g of 2,2,2-trifluoroethanol was added dropwise in a suspension of 0.33 g of 60% oily sodium hydride in 30 mL of tetrahydrofuran under cooling with ice and with stirring, and stirred at the same temperature for 10 minutes. Then, in this reaction mixture, the tetrahydrofuran solution of benzoic acid chloride prepared above was added dropwise under cooling with ice and with stirring. After the completion of the addition dropwise, it was continued to stir at room temperature for 1 hour. After the completion of the reaction, 50 mL of water was added in the reaction mixture, extracted with ethyl acetate (70 mL×1), the organic phase was dehydrated with and dried over saturated sodium chloride aqueous solution and then anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluated with ethyl acetate-hexane (2:3) to obtain 1.20 g of the aimed product as colorless resinous substance.

1. stirringstirred at the same temperature for 2 hours
2. distillationThen, the solvent was distilled off under reduced pressure
3. dissolutionthe residue was dissolved in 10 mL of tetrahydrofuran
4. addition1.50 g of 2,2,2-trifluoroethanol was added dropwise in a suspension of 0.33 g of 60% oily sodium hydride in 30 mL of tetrahydrofuran
5. temperatureunder cooling with ice
6. stirringwith stirring
7. stirringstirred at the same temperature for 10 minutes
8. customThen, in this reaction mixture, the tetrahydrofuran solution of benzoic acid chloride prepared
9. additionabove was added dropwise
10. temperatureunder cooling with ice
11. stirringwith stirring
12. additionAfter the completion of the addition dropwise
13. stirringto stir at room temperature for 1 hour
14. additionwas added in the reaction mixture
15. extractionextracted with ethyl acetate (70 mL×1)
16. dry with materialdried over saturated sodium chloride aqueous solution
17. distillationanhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure
18. customThe residue was purified with silica gel column chromatography that