4-Iodophenol → Methyl 5-[(4-iodophenoxy)methyl]furan-2-carboxylate

HRID 643776Notes

Reaction equation

HRID 643776 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:11][O:12][C:13]([C:15]1[O:16][C:17]([CH2:20]Cl)=[CH:18][CH:19]=1)=[O:14]>CN(C)C=O>[CH3:11][O:12][C:13]([C:15]1[O:16][C:17]([CH2:20][O:8][C:5]2[CH:6]=[CH:7][C:2]([I:1])=[CH:3][CH:4]=2)=[CH:18][CH:19]=1)=[O:14]

Participants

5

Reactant 3

HCID 108944-IodophenolHCID 24758Sodium hydrideHCID 75065Methyl 5-(chloromethyl)-2-furoate

Product 1

HCID 997605Methyl 5-[(4-iodophenoxy)methyl]furan-2-carboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
5 °C

Procedure

A solution of 4-iodophenol (10.08 g, 45.8 mmol) in N,N-dimethylformamide (30 mL) was added to a ice-bath cooled suspension of sodium hydride (60%; 1.65 g, 41.2 mmol) in N,N-dimethylformamide (30 mL). The ice bath was removed and the mixture was stirred for 1 h. The mixture was cooled again to ˜5° C. and a solution of 5-(chloro-methyl)-furan-2-carboxylic acid methyl ester (4.00 g, 22.9 mmol) in N,N-dimethylformamide (60 mL) was added. The reaction mixture was stirred overnight at room temperature, then the solvents were evaporated under reduced pressure and water was added. The mixture was extracted three times with ethyl acetate and the combined organic layers were washed twice with 1 M NaOH, and once each with water and brine. The organic solution was dried (magnesium sulfate) filtered, evaporated, and purified using a Biotage 65 L purification system, eluting with 3% methylene chloride/toluene to give 5-(4-iodo-phenoxymethyl)-furan-2-carboxylic acid methyl ester (2.3 g, 28%) as a white solid, along with some mixed fractions.

Workup

  1. temperaturecooled
  2. customThe ice bath was removed
  3. stirringThe reaction mixture was stirred overnight at room temperature
  4. customthe solvents were evaporated 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 twice with 1 M NaOH
  8. dry with materialThe organic solution was dried (magnesium sulfate)
  9. filtrationfiltered
  10. customevaporated
  11. custompurified
  12. customa Biotage 65 L purification system
  13. washeluting with 3% methylene chloride/toluene

Sources & evidence

ORD record
ord-e266bdad59cc47679360c89c19cafd16
Source dataset
uspto-grants-2010_04
Patent number
US07700632B2

Reaction notes

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