5-Benzyloxyindole → 3-(5-Benzyloxyindolyl)propanic acid

HRID 1295111

反応式

HRID 1295111 の反応式
[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

参加物

5

反応物 3

HCID 146245-BenzyloxyindoleHCID 24758Sodium hydride2 回HCID 79040Ethyl 2-bromopropionate2 回

生成物 1

HCID 668189953-(5-Benzyloxyindolyl)propanic acid

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a907fca6d289420cb30ce6797212ef09
出典データセット
uspto-grants-2007_07
特許番号
US07241789B2

関連ノート

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