5-苄氧基吲哚 → 3-(5-Benzyloxyindolyl)propanic acid

HRID 23976

反应方程式

HRID 23976 反应方程式
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH:21]([CH3:27])[C:22]([O:24]CC)=[O:23]>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([CH2:27][CH2:21][C:22]([OH:24])=[O:23])=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参与物

5

反应物 3

HCID 146245-苄氧基吲哚HCID 24758氢化钠2 次HCID 790402-溴丙酸乙酯2 次

产物 1

HCID 668189953-(5-Benzyloxyindolyl)propanic acid

试剂、催化剂与溶剂 1

HCID 6228N,N-二甲基甲酰胺溶剂

实验过程

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).

后处理

  1. stirringthe mixture was stirred at ambient temperature for 1 h
  2. stirringAfter stirring for 10 minutes
  3. stirringThe mixture was stirred at ambient temperature overnight
  4. customThe solvent was removed under high vacuum
  5. dissolutionthe residue was dissolved in water (10 mL)
  6. additiontetrahydrofuran (10 mL), NaOH (500 mg) was added
  7. stirringstirred for 2 h
  8. extractionthe mixture was extracted with methylene chloride
  9. washThe methylene chloride layer was washed with brine
  10. dry with materialdried over Na2SO4
  11. customAfter evaporating the solvent in vacuo
  12. customthe residue was purified by flash column chromatography (1-5% ethyl acetate in methylene chloride)

来源与证据

ORD记录
ord-6ae6446d60e540eca7b280236ddbdf35
来源数据集
uspto-grants-2005_02
专利号
US06855722B2

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