Ethanol → Methyl 2-[(5-benzofuranyloxy)methyl]benzoate

HRID 1070470Notes

Reaction equation

HRID 1070470 reaction equation
Br[CH2:2][C:3]1[C:4]([C:9]([O:11][CH3:12])=[O:10])=[CH:5][CH:6]=[CH:7][CH:8]=1.[C:13](=[O:16])([O-])[O-].[K+].[K+].[CH2:19]([OH:21])[CH3:20]>C(OCC)(=O)C.O.[C].[Pd]>[O:21]1[C:3]2[CH:4]=[CH:5][C:13]([O:16][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[C:9]([O:11][CH3:12])=[O:10])=[CH:7][C:8]=2[CH:20]=[CH:19]1.[O:21]1[C:3]2[CH:4]=[CH:5][C:13]([O:16][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[C:9]([O:11][CH3:12])=[O:10])=[CH:7][C:8]=2[CH2:20][CH2:19]1

Participants

8

Reactant 3

HCID 702EthanolHCID 11430Potassium CarbonateHCID 2734813Methyl 2-(bromomethyl)benzoate

Product 2

HCID 22397060HCID 22397060, compoundYield 17%HCID 22397069Methyl 2-[(5-benzofuranyloxy)methyl]benzoateYield 27%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
100 °C

Procedure

5-(Benzyloxy)benzofuran (1.02 g, 4.55 mmol) obtained in Preparation Example 2-4, Step 2 was dissolved in a mixed solvent of ethanol (5 ml) and ethyl acetate (5 ml) and 5% palladium carbon (500 mg) was added, which was followed by hydrogenation at room temperature under normal pressure. After 2 hr, the reaction mixture was passed through celite and the filtrate was concentrated under reduced pressure. The residue was dissolved in dimethylformamide (20 ml) and methyl α-bromo-o-toluate (1.042 g, 4.55 mmol) and potassium carbonate (1.26 g, 9.10 mmol) were added. The mixture was heated at 100° C. for 1.25 hr and cooled to room temperature. The reaction mixture was diluted with water and ethyl acetate to separate the layers. The organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to give methyl 2-[(5-benzofuranyloxy)methyl]benzoate (352 mg, 27%, white crystals) and methyl 2-[(2,3-dihydrobenzofuran-5-yloxy)methyl]benzoate (220 mg, 17%, pale-yellow oil).

Workup

  1. additionwas added
  2. customwas followed by hydrogenation at room temperature under normal pressure
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in dimethylformamide (20 ml)
  5. temperaturecooled to room temperature
  6. customto separate the layers
  7. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1)

Sources & evidence

ORD record
ord-103b8f5582974fff85c8a333a754cb11
Source dataset
uspto-grants-2005_06
Patent number
US06903094B2

Reaction notes

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