Sodium Chloride → 4-Ethoxy-2-fluoro-1-(phenylmethoxy)benzene

HRID 1931568Notes

Reaction equation

HRID 1931568 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][C:12]=1[F:18])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.I[CH2:20][CH3:21].[Cl-].[Na+]>CN(C)C=O>[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:20][CH3:21])=[CH:13][C:12]=1[F:18])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 14903134-(Benzyloxy)-3-fluorophenol

Product 1

HCID 669153164-Ethoxy-2-fluoro-1-(phenylmethoxy)benzeneYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion; 55 mg, 1.38 mmol) was added to a mixture of 4-benzyloxy-3-fluoro-phenol (Bionet Research, Camelford, Cornwall, UK; 250 mg, 1.15 mmol) in dimethylformamide (4 mL). After stirring for 15 min, iodoethane (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 215 mg, 1.38 mmol) was added and the reaction mixture was stirred overnight. Saturated sodium chloride was added to quench the reaction and the aqueous layer was extracted three times with ethyl acetate. The combined organic extracts were washed with saturated ammonium chloride and saturated sodium carbonate, and then dried over sodium sulfate. The mixture was filtered, concentrated and purified by flash chromatography on silica gel, eluting with 5% ethyl acetate/hexane to give 1-benzyloxy-4-ethoxy-2-fluoro-benzene (270 mg, 96%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 1.26 (t, 3H, J=7.0 Hz), 3.93 (q, 2H, J=7.0 Hz), 5.07 (s, 2H), 6.62-6.67 (m, 1H), 6.82-6.87 (m, 1H), 7.11 (t, 1H, J=9.0 Hz), 7.31-7.42 (m, 5H).

Workup

  1. stirringthe reaction mixture was stirred overnight
  2. customto quench
  3. customthe reaction
  4. extractionthe aqueous layer was extracted three times with ethyl acetate
  5. washThe combined organic extracts were washed with saturated ammonium chloride and saturated sodium carbonate
  6. dry with materialdried over sodium sulfate
  7. filtrationThe mixture was filtered
  8. concentrationconcentrated
  9. custompurified by flash chromatography on silica gel
  10. washeluting with 5% ethyl acetate/hexane

Sources & evidence

ORD record
ord-bc1fdaa8e45d47779d544bfac5ace69e
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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