Methyl 4-Formylbenzoate → Methyl 4-(4-(chloromethyl)-5-methyloxazol-2-yl)benzoate

HRID 2221566Notes

Reaction equation

HRID 2221566 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1)=[O:2].[CH3:13][C:14](=[N:18]O)[C:15](=O)[CH3:16].[ClH:20].C(OCC)(=O)C>>[Cl:20][CH2:13][C:14]1[N:18]=[C:1]([C:3]2[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=2)[O:2][C:15]=1[CH3:16]

Participants

4

Reactant 3

HCID 15294Methyl 4-FormylbenzoateHCID 63989692-Oxime 2,3-butanedioneHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 23076573Methyl 4-(4-(chloromethyl)-5-methyloxazol-2-yl)benzoateYield 42%

Procedure

A mixture of methyl 4-formylbenzoate (1.63 g), 2,3-butanedione-2-oxime (1.0 g) and 4N hydrogenchloride-ethyl acetate solution (10 mL) was stirred at room temperature for 4 days. After concentration of the reaction mixture, the obtained crystals were washed with diethyl ether. Tetrahydrofuran (30 mL) was added to the crystals, and thionyl chloride (1.90 g) was further added. The mixture was heated under reflux for 3 hrs. After concentration of the reaction mixture, saturated aqueous sodium hydrogen carbonate was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give methyl 4-(4-chloromethyl-5-methyl-1,3-oxazol-2-yl)benzoate as colorless crystals (1.10 g, 42%) from a fraction eluted with ethyl acetate-hexane (1:3, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 130-131° C.

Workup

  1. washAfter concentration of the reaction mixture, the obtained crystals were washed with diethyl ether
  2. additionTetrahydrofuran (30 mL) was added to the crystals, and thionyl chloride (1.90 g)
  3. additionwas further added
  4. temperatureThe mixture was heated
  5. temperatureunder reflux for 3 hrs
  6. additionAfter concentration of the reaction mixture, saturated aqueous sodium hydrogen carbonate was added to the residue
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe ethyl acetate layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-a62d5424342c42e6bfa84be5157ea4a8
Source dataset
uspto-grants-2008_05
Patent number
US07368578B2

Reaction notes

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