Sodium hydride → (3-Amino-4-fluorophenoxy)acetic acid methyl ester

HRID 2266561Notes

Reaction equation

HRID 2266561 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].[H-].[Na+].[CH3:12][O:13][C:14](=[O:17])[CH2:15]Br>CN(C)C=O.[Cl-].[NH4+]>[CH3:12][O:13][C:14](=[O:17])[CH2:15][O:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([NH2:1])[CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 135191803-Amino-4-fluorophenol

Product 1

HCID 66717607(3-Amino-4-fluorophenoxy)acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

3-Amino-4-fluorophenol (3.0 g) was added to a stirred suspension of sodium hydride (60% in oil, 0.94 g) in N,N-dimethylformamide (30 mL) at 0° C. The mixture was warmed to room temperature for 15 minutes and then cooled to 0° C. and this mixture was treated with bromoacetic acid methyl ester (3.3 g). The resulting mixture was warmed to room temperature and then stirred at this temperature for 2 hours. The mixture was diluted with dilute aqueous ammonium chloride solution and extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was removed under reduced pressure and purification of the residue by column chromatography on silica gel, eluting with a mixture of toluene, dichloromethane and ethyl acetate (2:1:0 to 0:1:0 to 0:20:1 by volume) gave title compound, 2.7 g.

Workup

  1. temperaturecooled to 0° C.
  2. temperatureThe resulting mixture was warmed to room temperature
  3. extractionextracted with ethyl acetate
  4. washThe combined extracts were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was removed under reduced pressure and purification of the residue by column chromatography on silica gel
  7. washeluting with a mixture of toluene, dichloromethane and ethyl acetate (2:1:0 to 0:1:0 to 0:20:1 by volume)

Sources & evidence

ORD record
ord-04c003b666c44493943d408acf38cbff
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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