反应详情

To a solution of 2-[(4-fluorobenzoylamino)acetyl]thiophene (527 mg) in N,N-dimethylformamide (10 ml) was added sodium hydride (88 mg, 60% mineral oil) under ice-cooling, and the mixture was stirred under argon atmosphere at room temperature for one hour. After ice-cooling, acrylonitrile (127 ml) was added to the mixture and the mixture was stirred at room temperature for 3 hours. After addition of ice-water, the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (10 ml), and phosphoryl chloride (240 μl) was added to the solution under ice-cooling. The mixture was stirred under argon atmosphere at room temperature for 3 hours. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, the mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane:ethyl acetate=9:1→7:1), and triturated with hexane and ethyl acetate to obtain 4-(2-cyanoethyl)-2-(4-fluorophenyl)-5-(2-thienyl)oxazole (132 mg) as colorless powder.

1. temperaturecooling
2. temperatureAfter ice-cooling
3. stirringthe mixture was stirred at room temperature for 3 hours
4. extractionthe mixture was extracted with ethyl acetate
5. washThe organic layer was washed with water and brine
6. dry with materialdried over anhydrous sodium sulfate
7. customthe solvent was removed under reduced pressure
8. dissolutionThe resulting residue was dissolved in N,N-dimethylformamide (10 ml)
9. additionphosphoryl chloride (240 μl) was added to the solution under ice-
10. temperaturecooling
11. stirringThe mixture was stirred under argon atmosphere at room temperature for 3 hours
12. additionTo the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution
13. extractionthe mixture was extracted with ethyl acetate
14. dry with materialdried over anhydrous sodium sulfate
15. customthe solvent was removed under reduced pressure
16. customThe resulting residue was purified by silica gel column chromatography (solvent: hexane:ethyl acetate=9:1→7:1)
17. customtriturated with hexane and ethyl acetate