Dimethylformamide → 2-Methoxy-5-(2-oxo-propoxy)-benzoic acid methyl ester

HRID 2230728Notes

Reaction equation

HRID 2230728 reaction equation
O[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.Cl[CH2:15][C:16](=[O:18])[CH3:17].C(=O)([O-])[O-:20].[K+].[K+].CN(C)C=O>C(OCC)(=O)C>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:10]=[C:11]([O:20][CH2:15][C:16](=[O:18])[CH3:17])[CH:2]=[CH:3][C:4]=1[O:12][CH3:13]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6571ChloroacetoneHCID 11430Potassium CarbonateHCID 12532676Methyl 4-hydroxy-2-methoxybenzoate

Product 1

HCID 701488462-Methoxy-5-(2-oxo-propoxy)-benzoic acid methyl esterYield 102.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Stir a mixture of methyl 4-hydroxy-2-methoxybenzoate (Danishefsky et al., J. Med. Chem. 1979, 101, 7001-7008, 0.54 g, 3 mmol), chloroacetone (6 mmol, Aldrich Chemical Company), potassium carbonate (9 mmol) and dimethylformamide at 50° C. overnight. Cool the reaction to room temperature, dilute with ethyl acetate, wash with saturated NaHCO3 solution and saturated brine. Dry (MgSO4) the organic phase, filter and concentrate the filtrate in vacuo. Purify the residue by column chromatography (silica gel, step gradient elution with 10% ethyl acetate in hexane to 30% ethyl acetate in hexane) and concentrate the appropriate fractions to afford 0.73 g of 2-methoxy-5-(2-oxo-propoxy)-benzoic acid methyl ester.

Workup

  1. temperatureCool
  2. customthe reaction to room temperature
  3. washwash with saturated NaHCO3 solution and saturated brine
  4. dry with materialDry (MgSO4) the organic phase
  5. filtrationfilter
  6. concentrationconcentrate the filtrate in vacuo
  7. customPurify the residue
  8. washby column chromatography (silica gel, step gradient elution with 10% ethyl acetate in hexane to 30% ethyl acetate in hexane)
  9. concentrationconcentrate the appropriate fractions

Sources & evidence

ORD record
ord-1581841cd0e24037afa5288adb5d6351
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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