Sodium hydride → HCID 69449296, compound

HRID 2205411Notes

Reaction equation

HRID 2205411 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4].[F:14][CH:15]([F:25])[O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Br)=[CH:19][CH:18]=1.[H-].[Na+]>CN(C=O)C.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][N:11]2[CH2:21][C:20]2[CH:19]=[CH:18][C:17]([O:16][CH:15]([F:14])[F:25])=[CH:24][CH:23]=2)=[CH:7][CH:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 639844Methyl indole-6-carboxylateHCID 27370014-(Difluoromethoxy)benzyl Bromide

Product 1

HCID 69449296HCID 69449296, compoundYield 21.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of commercially available 1H-indole-6-carboxylic acid methyl ester (0.35 g, 2.0 mmol) and 4-difluoromethoxy-benzyl bromide (0.52 g, 2.2 mmol) in DMF (2 mL) was added sodium hydride (92 mg, 2.3 mmol). After stirring at room temperature for 3.5 hr, the solution was diluted with water (25 mL) and ethyl acetate (75 mL), the organic layer was washed again with dilute NaHCO3 (25 mL) and then brine (25 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The remaining residue was subjected to flash chromatography (ethyl acetate/hexane, 1:5) to provide 1-(4-difluoromethoxy-phenylmethyl)-1H-indole-6-carboxylic acid methyl ester as a colorless oil (0.14 g, 21% yield).

Workup

  1. washthe organic layer was washed again with dilute NaHCO3 (25 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-ed05d5d4067f45f7afd5dc19b5c1b0ba
Source dataset
uspto-grants-2016_06
Patent number
US09371281B2

Reaction notes

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