Benzyl Bromide → 1-Bromo-3-benzyloxy-4,5-difluorobenzene

HRID 602053Notes

Reaction equation

HRID 602053 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([F:9])=[C:6]([OH:8])[CH:7]=1.C([O-])([O-])=O.[K+].[K+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CCN(CC)CC>CCOC(C)=O.O.CN(C=O)C>[Br:1][C:2]1[CH:7]=[C:6]([O:8][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]([F:9])=[C:4]([F:10])[CH:3]=1

Participants

8

Reactant 4

HCID 7498Benzyl BromideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 27733075-Bromo-2,3-Difluorophenol

Product 1

HCID 574706011-Bromo-3-benzyloxy-4,5-difluorobenzeneYield 0.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of DMF (100 mL), 5-bromo-2,3-difluorophenol (10 g, 47.85 mol), and K2CO3 (7.27 g, 52.63 mol) and benzyl bromide (9 g, 52.63 mol) were combined at 0° C. under N2. The solution was allowed to warm to rt and stirred overnight. H2O, Et3N (2 eq) and EtOAc (5000 mL) were added and the organic layer separated. The aqueous layer was washed with EtOAc (2×) and the combined organic fractions were washed with 1M HCl (2×), sat. aq. NaHCO3 (2×), dried, and concentrated. The crude product was purified by Biotage (gradient 100% hexanes-60% EtOAc/hexanes) to afford 10.08 g of product as an oil.

Workup

  1. customwere combined at 0° C. under N2
  2. customthe organic layer separated
  3. washThe aqueous layer was washed with EtOAc (2×)
  4. washthe combined organic fractions were washed with 1M HCl (2×), sat. aq. NaHCO3 (2×)
  5. customdried
  6. concentrationconcentrated
  7. customThe crude product was purified by Biotage (gradient 100% hexanes-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9499e05c84fc469890fe976704da6dab
Source dataset
uspto-grants-2011_03
Patent number
US07902394B2

Reaction notes

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