5-Benzyloxyindole → 5-Benzyloxy-indol-1-yl-propionic acid methyl ester

HRID 734387Notes

Reaction equation

HRID 734387 reaction equation
[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]([CH3:26])[C:22]([O:24][CH3:25])=[O:23]>CN(C=O)C>[CH3:25][O:24][C:22](=[O:23])[CH:21]([N:14]1[C:15]2[C:11](=[CH:10][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:17][CH:16]=2)[CH:12]=[CH:13]1)[CH3:26]

Participants

5

Reactant 3

HCID 146245-BenzyloxyindoleHCID 24758Sodium hydrideHCID 95576Methyl 2-bromopropionate

Product 1

HCID 578454965-Benzyloxy-indol-1-yl-propionic acid methyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-benzyloxyindole (13.5 g, 60.46 mmol) in DMF (300 mL) was added sodium hydride (60% dispersion in mineral oil, 3.63 g, 90.7 mmol). The resulting suspension was stirred at rt for 1 h after which methyl 2-bromopropionate (11.1 g, 66.51 mmol) was added. The resulting suspension was stirred at rt for 6 h. The reaction mixture was quenched with sat. aqueous ammonium chloride solution (25 mL), and diluted with 200 mL of EtOAc. The organic layer was washed with water three times. The aqueous layer was extracted again with EtOAc. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated via rotary evaporation. The resulting brown oil was purified on silica gel (EtOAc/hexanes 1:1) to give the title compound as a brownish oil (15.3 g, 82%). LC/MS m/z 310 (M+H)+, RT 4.04 min. 1H NMR (400 MHz, Acetone-d6) δ 7.57 (d, 2H), 7.23-7.41 (m, 5H), 7.19 (d, 1H), 6.84 (d, 1H), 6.40 (d, 1H), 5.37 (q, 1H), 5.17 (s, 2H), 3.66 (s, 3H), 1.79 (d, 3H).

Workup

  1. additionwas added
  2. customThe reaction mixture was quenched with sat. aqueous ammonium chloride solution (25 mL)
  3. additiondiluted with 200 mL of EtOAc
  4. washThe organic layer was washed with water three times
  5. extractionThe aqueous layer was extracted again with EtOAc
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated via rotary evaporation
  9. customThe resulting brown oil was purified on silica gel (EtOAc/hexanes 1:1)

Sources & evidence

ORD record
ord-d8ed1532009e4e6fa105260aa2f3b58b
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

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