4-Hydroxybiphenyl → Methyl 5-[(4-phenylphenoxy)methyl]furan-2-carboxylate

HRID 899505Notes

Reaction equation

HRID 899505 reaction equation
[H-].[Na+].[C:3]1([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:16][O:17][C:18]([C:20]1[O:21][C:22]([CH2:25]Cl)=[CH:23][CH:24]=1)=[O:19]>CN(C)C=O>[CH3:16][O:17][C:18]([C:20]1[O:21][C:22]([CH2:25][O:15][C:12]2[CH:11]=[CH:10][C:9]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)=[CH:14][CH:13]=2)=[CH:23][CH:24]=1)=[O:19]

Participants

5

Reactant 3

HCID 71034-HydroxybiphenylHCID 24758Sodium hydrideHCID 75065Methyl 5-(chloromethyl)-2-furoate

Product 1

HCID 586917Methyl 5-[(4-phenylphenoxy)methyl]furan-2-carboxylateYield 47,491.199%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
-5 °C

Procedure

N,N-Dimethylformamide (400 mL) was added to sodium hydride (60% dispersion; ˜16 g, 0.4 mol) which had been washed with hexanes. The mixture was cooled to −5° C., and then a solution of 4-phenylphenol (73.12 g, 0.43 mmol) in N,N-dimethylformamide (150 mL) was added. The mixture was allowed to stir at room temperature for 2.5 h, and then a solution of 5-chloromethylfuran-2-carboxylic acid methyl ester (25 g, 0.14 mmol) in N,N-dimethylformamide (100 mL) was added. The reaction mixture was heated at ˜105° C. for 2 h, and then it was allowed to cool, evaporated under reduced pressure, and water was added. The mixture was extracted three times with ethyl acetate, and the combined organic layers were washed with saturated brine, dried (magnesium sulfate), filtered, evaporated, and purified using a Biotage 75 L purification system, eluting with 0-10% methylene chloride/toluene to give 5-(biphenyl-4-yloxymethyl)-furan-2-carboxylic acid methyl ester (20.5 g, 46%).

Workup

  1. washhad been washed with hexanes
  2. temperatureThe reaction mixture was heated at ˜105° C. for 2 h
  3. temperatureto cool
  4. customevaporated under reduced pressure, and water
  5. additionwas added
  6. extractionThe mixture was extracted three times with ethyl acetate
  7. washthe combined organic layers were washed with saturated brine
  8. dry with materialdried (magnesium sulfate)
  9. filtrationfiltered
  10. customevaporated
  11. custompurified
  12. customa Biotage 75 L purification system
  13. washeluting with 0-10% methylene chloride/toluene

Sources & evidence

ORD record
ord-528fee048c97496facfc1b0cdfdd2156
Source dataset
uspto-grants-2008_04
Patent number
US07355049B2

Reaction notes

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