反应详情

To a mixture of 1.14 g (4.40 mmol. ) of 2-amino- 3-(4-phenoxyphenoxy)propanol, 0.58 g (5.72 mmol.) of triethylamine and 20 ml of anhydrous tetrahydrofuran, there was added dropwise a solution of 0.78 g (4.40 mmol.) of 2,6-difluorobenzoylchloride in 10 ml of anhydrous tetrahydrofuran with stirring at a temperature of from 5° C. to 10° C. for 5 minutes. After addition, the reaction mixture was stirred at room temperature for 2 hours. The above mixture was filtrated with a filter glass to remove the resultant precipitate and the filtrate was concentrated under reduced pressure. To the residue, there was added 20 ml of toluene and 10 ml of thionyl chloride and the reaction mixture was refluxed by heating with stirring for 5 hours. The reaction mixture was cooled;to room temperature and concentrated under reduced pressure. To the residue, there was added 20 ml of methanol and further added dropwise 1 ml of a 5N aqueous solution of sodium hydroxide with stirring at a temperature of 60° C. for 5 minutes. Then the reaction mixture was stirred at the same temperature for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. To the residue, there was added 100 ml of ethyl acetate. The mixture was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography to give 1.28 g of 2-(2,6-difluorophenyl)-4-[(4-phenoxyphenoxy)methyl]-2-oxazoline as a colorless oily substance (nD19.1 1.5814).

1. additionAfter addition
2. stirringthe reaction mixture was stirred at room temperature for 2 hours
3. filtrationThe above mixture was filtrated with a filter glass
4. customto remove the resultant precipitate
5. concentrationthe filtrate was concentrated under reduced pressure
6. additionTo the residue, there was added 20 ml of toluene and 10 ml of thionyl chloride
7. temperaturethe reaction mixture was refluxed
8. temperatureby heating
9. stirringwith stirring for 5 hours
10. customwas cooled;to room temperature
11. concentrationconcentrated under reduced pressure
12. additionTo the residue, there was added 20 ml of methanol
13. additionfurther added dropwise 1 ml of a 5N aqueous solution of sodium hydroxide
14. stirringwith stirring at a temperature of 60° C. for 5 minutes
15. stirringThen the reaction mixture was stirred at the same temperature for 5 hours
16. concentrationconcentrated under reduced pressure
17. additionTo the residue, there was added 100 ml of ethyl acetate
18. washThe mixture was washed with water
19. dry with materialdried over anhydrous magnesium sulfate
20. concentrationconcentrated under reduced pressure