تفاعل #653183

معادلة التفاعل

sulfuric acid

4-ethylbromobenzene

n-butyllithium

ethyl 7-bromo-2,3-dihydro-1-benzoxepine-4-carboxylate

4-ethylphenyl borate

potassium carbonate

tributyl borate

→

ethyl 7-(4-ethylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylate

المردود 85.5%

المذيبات

tetrahydrofuran

toluene-ethanol water

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGstirred at room temperature for 2 hours
2. 2
   workup.STIRRINGthe mixture was stirred for 1 hour
3. 3
   استخلاصThe mixture was extracted with ethyl acetate
4. 4
   غسيلThe organic layer was washed with saturated sodium chloride solution
5. 5
   تجفيفdried with magnesium sulfate
6. 6
   تركيزconcentrated under reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in acetone (30 ml)
8. 8
   workup.ADDITIONto the mixture was added 10% sulfuric acid (50 ml)
9. 9
   workup.STIRRINGThe mixture was stirred at room temperature for 16 hours
10. 10
    أخرىunder reduced pressure acetone was evaporated
11. 11
    استخلاصThe mixture was extracted with ethyl acetate
12. 12
    غسيلThe organic layer was washed with saturated sodium chloride solution
13. 13
    تجفيفdried with magnesium sulfate
14. 14
    تركيزconcentrated under reduced pressure
15. 15
    أخرىThe residue was separated
16. 16
    أخرىpurified with column chromatography (ethyl acetate/hexane=1:2)
17. 17
    أخرىto give crude 4-ethylphenyl borate (0.91 g) as colorless solid
18. 18
    درجة الحرارةthe mixture was refluxed for 18 hours
19. 19
    درجة الحرارةcooled to room temperature
20. 20
    غسيلThe organic layer was washed with saturated sodium chloride solution
21. 21
    تجفيفdried with magnesium sulfate
22. 22
    تركيزconcentrated under reduced pressure
23. 23
    أخرىThe residue was separated
24. 24
    أخرىpurified with column chromatography (ethyl acetate/hexane=1:15)

الإجراء التجريبي

Under argon atmosphere, to a solution of 4-ethylbromobenzene (10.0 g) in tetrahydrofuran (60 ml) was added n-butyllithium (1.6M hexane solution) (37.2 ml) at −78° C., and the mixture was stirred for 1 hour. To the reaction mixture was dropwise added a solution of tributyl borate (13.68 g) in tetrahydrofuran (30 ml), and the reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours. To the reaction mixture was added 10% sulfuric acid (100 ml), and the mixture was stirred for 1 hour. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in acetone (30 ml), and to the mixture was added 10% sulfuric acid (50 ml). The mixture was stirred at room temperature for 16 hours, and under reduced pressure acetone was evaporated. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:2) to give crude 4-ethylphenyl borate (0.91 g) as colorless solid. Under argon atmosphere, a solution of ethyl 7-bromo-2,3-dihydro-1-benzoxepine-4-carboxylate (500 mg), the above crude 4-ethylphenyl borate (0.32 g) and potassium carbonate (0.49 g) in toluene-ethanol-water (20-2-2 ml) was stirred at room temperature for 1 hour. To the reaction mixture was added tetrakistriphenyl-phosphinepalladium (0.06 g), and the mixture was refluxed for 18 hours and cooled to room temperature. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:15) to give ethyl 7-(4-ethylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylate (464 mg) as colorless crystals.

المصدر