Sodium hydride → Methyl 6-(5-benzyloxy-6-chloro-2-phenylindol-1-ylmethyl)pyridine-2-carboxylate

HRID 1191665Notes

Reaction equation

HRID 1191665 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1[Cl:18])[NH:14][C:13]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH2:28][C:29]1[N:34]=[C:33]([C:35]([O:37][CH3:38])=[O:36])[CH:32]=[CH:31][CH:30]=1.[Cl-].[NH4+]>CN(C)C=O.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1[Cl:18])[N:14]([CH2:28][C:29]1[N:34]=[C:33]([C:35]([O:37][CH3:38])=[O:36])[CH:32]=[CH:31][CH:30]=1)[C:13]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 53404482Methyl 6-(chloromethyl)pyridine-2-carboxylateHCID 69671085HCID 69671085, compound

Product 1

HCID 69670868Methyl 6-(5-benzyloxy-6-chloro-2-phenylindol-1-ylmethyl)pyridine-2-carboxylateYield 61.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-benzyloxy-6-chloro-2-phenylindole (513 mg) in N,N-dimethylformamide (7.7 mL) was added sodium hydride (in oil, 50 to 72%, 92 mg) under cooling with ice under an argon atmosphere, and the mixture was stirred at room temperature for one hour. Then methyl 6-(chloromethyl)pyridine-2-carboxylate (342 mg) was added, and the mixture was stirred at 80° C. for 18 hours. The reaction mixture was allowed to cool to ambient temperature. A saturated aqueous ammonium chloride solution and water were added to the reaction mixture and this resulting mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (454 mg).

Workup

  1. temperatureunder cooling with ice under an argon atmosphere
  2. stirringthe mixture was stirred at 80° C. for 18 hours
  3. temperatureto cool to ambient temperature
  4. extractionthis resulting mixture was extracted with ethyl acetate
  5. washThe organic layer was washed successively with water and saturated saline
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-7aee65fca263464f860ff3d8d18711c7
Source dataset
uspto-grants-2014_03
Patent number
US08680120B2

Reaction notes

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