Sodium hydride → Methyl 2-fluoro-3-(2-furan-3-yl-5-methoxyindol-1-ylmethyl)benzoate

HRID 1191682Notes

Reaction equation

HRID 1191682 reaction equation
[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[NH:7][C:8]3[C:13]([CH:14]=2)=[CH:12][C:11]([O:15][CH3:16])=[CH:10][CH:9]=3)=[CH:2]1.[H-].[Na+].Br[CH2:20][C:21]1[C:22]([F:31])=[C:23]([CH:28]=[CH:29][CH:30]=1)[C:24]([O:26][CH3:27])=[O:25].[Cl-].[NH4+]>CN(C)C=O.ClCCl.CCCCCC>[F:31][C:22]1[C:21]([CH2:20][N:7]2[C:8]3[C:13](=[CH:12][C:11]([O:15][CH3:16])=[CH:10][CH:9]=3)[CH:14]=[C:6]2[C:3]2[CH:4]=[CH:5][O:1][CH:2]=2)=[CH:30][CH:29]=[CH:28][C:23]=1[C:24]([O:26][CH3:27])=[O:25]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 22050044Methyl 3-(bromomethyl)-2-fluorobenzoateHCID 696711462-Furan-3-yl-5-methoxyindole

Product 1

HCID 69670885Methyl 2-fluoro-3-(2-furan-3-yl-5-methoxyindol-1-ylmethyl)benzoateYield 20.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21226440Methylenechloride HexaneSolvent

Procedure

To a solution of 2-furan-3-yl-5-methoxyindole (200 mg) in N,N-dimethylformamide (4.7 mL) was added sodium hydride (dispersed in liquid paraffin, minimum 55%, 62 mg) under cooling with ice, and the mixture was stirred at room temperature for one hour. Then a solution of methyl 3-bromomethyl-2-fluorobenzoate (278 mg) in N,N-dimethylformamide (0.2 mL) was added, and the mixture was stirred at 80° C. for 15 hours. The reaction mixture was allowed to cool to ambient temperature. A saturated aqueous ammonium chloride solution-water (2/1) 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 aminopropylated silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (72 mg).

Workup

  1. temperatureunder cooling with ice
  2. stirringthe mixture was stirred at 80° C. for 15 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 aminopropylated silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-5b1b55b0c7df4cb9bbdc8ca0600bb995
Source dataset
uspto-grants-2014_03
Patent number
US08680120B2

Reaction notes

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