反应详情

A solution of (3E)-4-(4-tert-butylphenyl)-4-(5-chloro-6-methoxypyridin-2-yl)but-3-enenitrile obtained in Reference Example 4-13 (101 mg) in isopropanol (3 mL) was stirred at 105° C., during which a 50% hydroxylamine solution (0.1 mL) was added dropwise thereto. The mixture was stirred at the same temperature for two hours. The reaction solution was left to cool and then the solvent was evaporated under reduced pressure. Carbonyldiimidazole (72 mg) was added to a solution of the residue in 1,4-dioxane (3 mL), and the mixture was stirred at 120° C. for 30 minutes. Carbonyldiimidazole (55 mg) was further added and the mixture was stirred at 140° C. for 30 minutes. The reaction solution was left to cool and then water was added, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and filtered, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=10:0→9:1) to give 3-[(2E)-3-(4-tert-butylphenyl)-3-(5-chloro-6-methoxypyridin-2-yl)prop-2-en-1-yl]-1,2,4-oxadiazol-5(2H)-one as an orange oil (73 mg, 62%).

1. additionwas added dropwise
2. waitThe reaction solution was left
3. temperatureto cool
4. customthe solvent was evaporated under reduced pressure
5. additionCarbonyldiimidazole (72 mg) was added to a solution of the residue in 1,4-dioxane (3 mL)
6. stirringthe mixture was stirred at 120° C. for 30 minutes
7. additionCarbonyldiimidazole (55 mg) was further added
8. stirringthe mixture was stirred at 140° C. for 30 minutes
9. waitThe reaction solution was left
10. temperatureto cool
11. additionwater was added
12. extractionfollowed by extraction with ethyl acetate
13. washThe organic layer was washed with brine
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. customafter which the solvent was evaporated under reduced pressure
17. customThe residue was purified by silica gel column chromatography (chloroform:methanol=10:0→9:1)