Benzyl Bromide → Ethyl 3-[3-(benzyloxy)-4,5-difluorophenyl]propanoate

HRID 602065Notes

Reaction equation

HRID 602065 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:5]=[C:6]([OH:9])[C:7]=1[F:8].C([O-])([O-])=O.[K+].[K+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.N(CC)CC>CCOC(C)=O.O.CN(C=O)C>[CH2:23]([O:9][C:6]1[CH:5]=[C:4]([CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=[C:2]([F:1])[C:7]=1[F:8])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 7498Benzyl BromideHCID 8021DiethylamineHCID 11430Potassium CarbonateHCID 57470570Ethyl 3-(3,4-difluoro-5-hydroxyphenyl)propanoate

Product 1

HCID 57470612Ethyl 3-[3-(benzyloxy)-4,5-difluorophenyl]propanoateYield 138.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of DMF (21 mL), ethyl 3-(3,4-difluoro-5-hydroxyphenyl)propanoate (2.46 g, 0.0107 mol), and K2CO3 (1.92 g, 0.0139 mol) were combined at 0° C. under N2. After 10 min, benzyl bromide (1.65 mL, 0.0139 mol) was added dropwise. The solution was allowed to warm to room temperature. After 16 h, H2O (50 mL), Et2NH (2 eq) and EtOAc (50 mL) were added and the organic layer isolated. 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 flash chromatography (gradient 100% hexanes-60% EtOAc/hexanes) to afford 4.74 g of product as an oil (86%).

Workup

  1. customwere combined at 0° C. under N2
  2. waitAfter 16 h
  3. customthe organic layer isolated
  4. washThe aqueous layer was washed with EtOAc (2×)
  5. washthe combined organic fractions were washed with 1M HCl (2×), sat. aq. NaHCO3 (2×)
  6. customdried
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (gradient 100% hexanes-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a30b0c14d0bc4d3e98a8b3b4789c2444
Source dataset
uspto-grants-2011_03
Patent number
US07902394B2

Reaction notes

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