Sodium hydride → HCID 67684773, compound

HRID 2400273Notes

Reaction equation

HRID 2400273 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[CH:6]2.[H-].[Na+].Cl[CH2:21][C:22]1[N:27]=[C:26]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[CH:24][CH:23]=1.[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:21][C:22]1[N:27]=[C:26]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[CH:24][CH:23]=1)[C:7]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[CH:6]2

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2928505-methoxy-2-phenyl-1H-indoleHCID 53404482Methyl 6-(chloromethyl)pyridine-2-carboxylate

Product 1

HCID 67684773HCID 67684773, compoundYield 9.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under an argon atmosphere, to a solution of 5-methoxy-2-phenyl-1H-indole (582 mg) in N,N-dimethylformamide (13 mL) was added sodium hydride (dispersed in liquid paraffin, 55% or more, 171 mg) under ice-cooling. This mixture was stirred for 5 minutes under ice-cooling, and then stirred for 30 minutes at room temperature. Subsequently, methyl 6-chloromethylpyridine-2-carboxylate (483 mg) was added thereto, followed by stirring at 80° C. for 18 hours. The reaction mixture was poured into an ice-cooled saturated aqueous ammonium chloride solution, and then ethyl acetate was added to the mixture to separate the organic layer. The aqueous layer was extracted twice with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (91 mg). 1H-NMR (CDCl3) δ ppm: 3.87 (3H, s), 4.02 (3H, s), 5.58 (2H, s), 6.60-6.75 (2H, m), 6.81 (1H, dd, J=2.5, 8.8 Hz), 7.02 (1H, d, J=8.8 Hz), 7.15 (1H, d, J=2.5 Hz), 7.30-7.45 (5H, m), 7.60-7.70 (1H, m), 7.95-8.05 (1H, m).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringstirred for 30 minutes at room temperature
  4. stirringby stirring at 80° C. for 18 hours
  5. customto separate the organic layer
  6. extractionThe aqueous layer was extracted twice with ethyl acetate
  7. washThe combined organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-fb2e6da87afc46338470f5a550d0d1ee
Source dataset
uspto-grants-2014_08
Patent number
US08796247B2

Reaction notes

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