反应详情

温度

0 °C

A mixture of sodium methoxide (15.5 g), dimethyl carbonate (91 ml) and 7-(4-fluorophenyl)-1-tetralone (13.8 g) was refluxed for 30 minutes. The reaction mixture was cooled to 0° C., and to the mixture was gradually added 3N hydrochloric acid (200 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in THF (90 ml), and to the mixture was added sodium boron hydride (1.36 g) at 0° C. and then was dropwise added methanol (9 ml) for 30 minutes. The reaction mixture was stirred at 0° C. for 4 hours, and to the mixture was added water (500 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, and concentrated under reduced pressure. The residue was dissolved in methanol (80 ml), and to the mixture was added 1N sodium hydroxide (100 ml). The mixture was refluxed for 4 hours and cooled to room temperature. The mixture was acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in Diglyme (50 ml), and to the mixture was added concentrated hydrochloric acid (10 ml). The mixture was stirred at 100° C. for 2 hours, and to the mixture was added water (500 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, and concentrated under reduced pressure. The residue was dissolved in 0.5N sodium hydroxide (400 ml), and the mixture was washed with diethylether. The aqueous layer was separated, acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give 7-(4-fluorophenyl)-3,4-dihydronaphthalene-2-carboxylic acid (6.01 g) as pale brown crystals.

1. temperaturewas refluxed for 30 minutes
2. extractionThe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with saturated sodium chloride solution
4. dry with materialdried with anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. dissolutionThe residue was dissolved in THF (90 ml)
7. additionto the mixture was added sodium boron hydride (1.36 g) at 0° C.
8. customfor 30 minutes
9. additionto the mixture was added water (500 ml)
10. extractionThe mixture was extracted with ethyl acetate
11. washThe organic layer was washed with saturated sodium chloride solution
12. concentrationconcentrated under reduced pressure
13. dissolutionThe residue was dissolved in methanol (80 ml)
14. additionto the mixture was added 1N sodium hydroxide (100 ml)
15. temperatureThe mixture was refluxed for 4 hours
16. temperaturecooled to room temperature
17. extractionextracted with ethyl acetate
18. washThe organic layer was washed with saturated sodium chloride solution
19. dry with materialdried with anhydrous sodium sulfate
20. concentrationconcentrated under reduced pressure
21. dissolutionThe residue was dissolved in Diglyme (50 ml)
22. additionto the mixture was added concentrated hydrochloric acid (10 ml)
23. stirringThe mixture was stirred at 100° C. for 2 hours
24. additionto the mixture was added water (500 ml)
25. extractionThe mixture was extracted with ethyl acetate
26. washThe organic layer was washed with saturated sodium chloride solution
27. concentrationconcentrated under reduced pressure
28. dissolutionThe residue was dissolved in 0.5N sodium hydroxide (400 ml)
29. washthe mixture was washed with diethylether
30. customThe aqueous layer was separated
31. extractionextracted with ethyl acetate
32. washThe organic layer was washed with saturated sodium chloride solution
33. dry with materialdried with anhydrous sodium sulfate
34. concentrationconcentrated under reduced pressure
35. customThe residue was recrystallized from ethyl acetate-diisopropylether