Benzyl Bromide → 2-Benzyloxy-4,6-difluoronitrobenzene

HRID 1372650Notes

Reaction equation

HRID 1372650 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-:11])=[O:10])=[C:4]([OH:12])[CH:3]=1.[H-].[Na+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C=O)C>[CH2:15]([O:12][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[C:5]=1[N+:9]([O-:11])=[O:10])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 118195353,5-Difluoro-2-nitrophenol

Product 1

HCID 178593022-Benzyloxy-4,6-difluoronitrobenzeneYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4,6-difluoro-2-hydroxynitrobenzene (12.5 g, 71.1 mmol) in DMF (150 ml) was added sodium hydride (60% in oil, 3.70 g, 92.4 mmol) under stirring at 0° C., and the reaction mixture was stirred for 15 minutes. Benzyl bromide (11.0 ml, 92.4 mmol) was added dropwise at 0° C. After completion of the dropwise addition, the reaction mixture was stirred at 80° C. for 18 hours. After cooling to room temperature, the mixture was poured in ice-1N HCl to neutralize therewith, followed by extraction with ether. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from ethyl acetate/hexane (1/5) eluate fractions, 2-benzyloxy-4,6-difluoronitrobenzene (13.7 g, 73%) was obtained as a yellow solid.

Workup

  1. stirringthe reaction mixture was stirred for 15 minutes
  2. additionAfter completion of the dropwise addition
  3. stirringthe reaction mixture was stirred at 80° C. for 18 hours
  4. temperatureAfter cooling to room temperature
  5. extractionfollowed by extraction with ether
  6. washThe extract was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationdistilled under reduced pressure
  9. customto remove the solvent
  10. customThe residue was purified by chromatography on a silica gel column, whereby from ethyl acetate/hexane (1/5) eluate fractions

Sources & evidence

ORD record
ord-12409e5ce9594de1be7decd1e2fdce22
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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