反应详情

To a stirred solution of 2-(4-hydroxyphenyl)ethanol (1.4 g) in tetrahydrofuran (30 ml) was added 60% sodium hydride in mineral oil (405 mg) under ice-cooling, and the mixture was stirred for 1 hour at room temperature. To the stirred reaction mixture was added chloromethyl methyl ether (770 μl) under ice-cooling, and the resulting mixture was stirred for 16 hours at room temperature. Additionally, to the stirred reaction mixture was added 60% sodium hydride in mineral oil (405 mg) under ice-cooling. After the mixture was stirred for 1 hour at room temperature, benzyl bromide (1.2 ml) was added under ice-cooling and the resulting mixture was stirred for 16 hours at room temperature. The reaction mixture was poured into ice-water and extracted with diethyl ether. The extract was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane (20 ml), trifluoroacetic acid (20 ml) was added to the solution under ice-cooling with stirring, and the mixture was stirred for 1 hour. After the reaction mixture was concentrated under reduced pressure, 2N aqueous sodium hydroxide solution (20 ml) and water (20 ml) were added to the residue, and the resulting mixture was vigorously shaken. The aqueous layer was separated, washed with diethyl ether, acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Purification of the residue by medium pressure liquid column chromatography on silica gel (eluent:hexane/diethyl ether=2/1) gave 4-(2-benzyloxyethyl)phenol (440 mg).

1. temperaturecooling
2. customTo the stirred reaction mixture
3. temperaturecooling
4. stirringthe resulting mixture was stirred for 16 hours at room temperature
5. customAdditionally, to the stirred reaction mixture
6. temperaturecooling
7. stirringAfter the mixture was stirred for 1 hour at room temperature
8. temperaturecooling
9. stirringthe resulting mixture was stirred for 16 hours at room temperature
10. extractionextracted with diethyl ether
11. washThe extract was washed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. customthe solvent was removed under reduced pressure
14. dissolutionThe residue was dissolved in dichloromethane (20 ml)
15. additiontrifluoroacetic acid (20 ml) was added to the solution under ice-
16. temperaturecooling
17. stirringwith stirring
18. stirringthe mixture was stirred for 1 hour
19. concentrationAfter the reaction mixture was concentrated under reduced pressure, 2N aqueous sodium hydroxide solution (20 ml) and water (20 ml)
20. additionwere added to the residue
21. stirringthe resulting mixture was vigorously shaken
22. customThe aqueous layer was separated
23. washwashed with diethyl ether
24. extractionextracted with ethyl acetate
25. washThe extract was washed with a saturated aqueous sodium bicarbonate solution and brine
26. dry with materialdried over anhydrous magnesium sulfate
27. customthe solvent was removed under reduced pressure
28. customPurification of the residue by medium pressure liquid column chromatography on silica gel (eluent:hexane/diethyl ether=2/1)