تفاعل #52254

معادلة التفاعل

sodium hydride

5-benzyloxyindole

sodium hydride

ethyl bromopropionate

ethyl bromopropionate

→

3-(5-benzyloxyindolyl)propanic acid

المذيبات

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe mixture was stirred at ambient temperature for 1 h
2. 2
   workup.STIRRINGAfter stirring for 10 minutes
3. 3
   workup.STIRRINGThe mixture was stirred at ambient temperature overnight
4. 4
   أخرىThe solvent was removed under high vacuum
5. 5
   workup.DISSOLUTIONthe residue was dissolved in water (10 mL)
6. 6
   workup.ADDITIONtetrahydrofuran (10 mL), NaOH (500 mg) was added
7. 7
   workup.STIRRINGstirred for 2 h
8. 8
   استخلاصthe mixture was extracted with methylene chloride
9. 9
   غسيلThe methylene chloride layer was washed with brine
10. 10
    تجفيفdried over Na2SO4
11. 11
    أخرىAfter evaporating the solvent in vacuo
12. 12
    أخرىthe residue was purified by flash column chromatography (1-5% ethyl acetate in methylene chloride)

الإجراء التجريبي

To a solution of 5-benzyloxyindole (1.15 g, 5 mmol) in N,N-dimethylformamide (40 mL) was added sodium hydride (200 mg, 5 mmol). After stirring for 30 minutes, ethyl bromopropionate (900 mg, 5.0 mmol) was added and the mixture was stirred at ambient temperature for 1 h, additional sodium hydride (100 mg, 2.5 mmol) was added. After stirring for 10 minutes, additional ethyl bromopropionate (180 mg, 1.0 mmol) was added. The mixture was stirred at ambient temperature overnight. The solvent was removed under high vacuum, the residue was dissolved in water (10 mL) and tetrahydrofuran (10 mL), NaOH (500 mg) was added and stirred for 2 h. After acidifying to pH 4-5, the mixture was extracted with methylene chloride. The methylene chloride layer was washed with brine and dried over Na2SO4. After evaporating the solvent in vacuo, the residue was purified by flash column chromatography (1-5% ethyl acetate in methylene chloride) to give 3-(5-benzyloxyindolyl)propanic acid as white solid. The solid was dissolved in N,N-dimethylformamide (20 mL), K2CO3 (1.0 g) and iodomethane (840 mg) were added and the reaction was stirred at ambient temperature for 3 h. The mixture was concentrated under high vacuum and residue was purified by flash column chromatography (methylene chloride) to give the title compound as a colorless oil (1.10 g, 71%). 1H-NMR (400 MHz, CDCl3) δ 7.47 (d, J=7.3 Hz, 2H), 7.38 (t, J=7.3 Hz, 2H), 7.32 (d, J=7.2 Hz, 1H), 7.23 (d, J=10.2 Hz, 1H), 7.15 (d, J=2.3 Hz, 1H), 7.09 (d, J=3.1 Hz, 1H), 6.96 (dd, J=8.8, 2.5 Hz, 1H), 6.39 (d, J=3.1 Hz, 1H), 5.10 (s, 2H), 4.41 (t, J=6.9 Hz, 2H), 3.66 (s, 3H), 2.81 (t, J=6.8 Hz, 2H).

المصدر