5-Benzyloxyindole → HCID 23159887, compound

HRID 2110885Notes

Reaction equation

HRID 2110885 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+].Cl[CH2:21][C:22]1[CH:41]=[CH:40][C:25]([CH2:26][O:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][C:36]([O:38]C)=[O:37])=[CH:30][CH:29]=2)=[CH:24][CH:23]=1.[OH-].[Na+]>CN(C)C=O.C(OCC)(=O)C.O1CCCC1.CO>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:21][C:22]1[CH:41]=[CH:40][C:25]([CH2:26][O:27][C:28]3[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[CH:30][CH:29]=3)=[CH:24][CH:23]=1)[CH:13]=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 146245-BenzyloxyindoleHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 23082857Methyl 3-(4-([4-(chloromethyl)benzyl]oxy)phenyl)propanoate

Product 1

HCID 23159887HCID 23159887, compoundYield 52.2%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(benzyloxy)-1H-indole (0.19 g, 0.86 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (60% in oil, 35 mg, 0.86 mmol) with stirring at 0° C., and the mixture was stirred at the same temperature for 10 min. Methyl 3-(4-{[4-(chloromethyl)benzyl]oxy}phenyl)propanoate (0.25 g, 0.78 mmol) was added to the obtained mixture and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate, and the mixture washed with 5% aqueous potassium hydrogensulfate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1) to give an oil. Then, a mixture of the obtained oil, 1 N aqueous sodium hydroxide solution (1.6 mL), methanol (3.0 mL) and tetrahydrofuran (6.0 mL) was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with 5% aqueous potassium hydrogensulfate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=1/2) to give the title compound (200 mg, yield 49%) as beige crystals. MS (APCI−): 490 (M−H).

Workup

  1. stirringthe mixture was stirred at the same temperature for 10 min
  2. stirringthe mixture was stirred at room temperature for 12 hr
  3. washthe mixture washed with 5% aqueous potassium hydrogensulfate solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1)
  7. customto give an oil
  8. stirringwas stirred at room temperature for 2 hr
  9. washthe mixture was washed with 5% aqueous potassium hydrogensulfate solution, water and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-4fb8160232564398aaf44a73620ee463
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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