Sodium hydride → (S)-2-(3-amino-4-fluorophenoxy)propionic acid methyl ester

HRID 2266625Notes

Reaction equation

HRID 2266625 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:18])[C@H:15](Cl)[CH3:16].[Cl-].[NH4+]>CN(C)C=O>[CH3:12][O:13][C:14](=[O:18])[C@@H:15]([O:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([NH2:1])[CH:3]=1)[CH3:16]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 149593Methyl 2-chloropropanoate, (R)-HCID 135191803-Amino-4-fluorophenol

Product 1

HCID 66717596(S)-2-(3-amino-4-fluorophenoxy)propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3-amino-4-fluorophenol (4.1 g) in N,N-dimethylformamide (15 mL) was added dropwise to a stirred suspension of sodium hydride (60% in oil, 1.3 g) in N,N-dimethylformamide (35 mL) at 0° C. The mixture was stirred a room temperature for 30 minutes, cooled 0° C. and then (R)-2-chloropropionic acid methyl ester (4.0 g) was added in one portion. The resulting mixture was stirred at room temperature overnight and then treated with saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate and the combined extracts, washed with saturated aqueous sodium chloride solution and then 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 dichloromethane and ethyl acetate (1:0 to 3:2 by volume) to give the mixture of title compounds as golden oil, 2.5 g.

Workup

  1. temperaturecooled 0° C.
  2. stirringThe resulting mixture was stirred at room temperature overnight
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe combined extracts, 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 dichloromethane and ethyl acetate (1:0 to 3:2 by volume)
  8. customto give
  9. additionthe mixture of title compounds as golden oil, 2.5 g

Sources & evidence

ORD record
ord-73de70f69d1346b78617fb468d731c1e
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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