Ethyl Acetate → 3-(2',4'-Difluoro-biphenyl-4-yloxymethyl)-benzoic acid methyl ester

HRID 1665233Notes

Reaction equation

HRID 1665233 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][CH:13]=2)[CH:5]=1.[F:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.O>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([C:24]3[CH:23]=[CH:22][C:21]([F:20])=[CH:26][C:25]=3[F:27])=[CH:14][CH:13]=2)[CH:5]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 57643351Methyl 3-((4-iodophenoxy)methyl)benzoate

Product 1

HCID 671503633-(2',4'-Difluoro-biphenyl-4-yloxymethyl)-benzoic acid methyl esterYield 94.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
102.5 °C

Procedure

Bis(tricyclohexylphosphine)palladium (250 mg, 0.375 mmol) was added to a stirred solution of 3-(4-iodo-phenoxymethyl)-benzoic acid methyl ester (4.6 g, 12.5 mmol) and 2,4-difluorophenylboronic acid (3.92 g, 25 mmol) in 125 mL dioxane. Argon was bubbled through the solution for 5 min. H2O (12.5 mL) was then added followed by dried, powdered potassium carbonate (3.45 g, 25 mmol). The mixture was heated to 100-105° C. under argon for 1 hr, cooled and distributed between 100 mL ethyl acetate and 100 mL H2O. The ethyl acetate layer was washed with saturated NaCl, dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography with a gradient of 0-5% ethyl acetate in hexanes to yield 4.2 g of 3-(2′,4′-difluoro-biphenyl-4-yloxymethyl)-benzoic acid methyl ester.

Workup

  1. customArgon was bubbled through the solution for 5 min
  2. additionH2O (12.5 mL) was then added
  3. customby dried
  4. temperaturecooled
  5. washThe ethyl acetate layer was washed with saturated NaCl
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography with a gradient of 0-5% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ea028e250bb74fad95b07ee405f867af
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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