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

HRID 1944272Notes

Reaction equation

HRID 1944272 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.[Cl-].[NH4+]>CN(C)C=O>[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 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 60984Methyl bromoacetateHCID 135191803-Amino-4-fluorophenol

Product 1

HCID 66717607(3-Amino-4-fluorophenoxy)acetic acid methyl esterYield 62.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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., and the resulting mixture was warmed to room temperature for 15 minutes. The mixture was cooled to 0° C. treated with bromoacetic acid methyl ester (3.3 g), and then stirred at room temperature for 2 hours. The mixture was treated with dilute aqueous ammonium chloride solution and extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and the solvent removed under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of toluene, dichloromethane and ethyl acetate (2:1:0, 0:1:0 to 0:20:1 by volume) gave title compound (2.7 g).

Workup

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

Sources & evidence

ORD record
ord-7680be6afcd443acbf0eed8888da5dfe
Source dataset
uspto-grants-2013_03
Patent number
US08394830B2

Reaction notes

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