Cesium fluoride → Methyl 2-fluoro-4-phenylbenzoate

HRID 2053693Notes

Reaction equation

HRID 2053693 reaction equation
[F:1][C:2]1[CH:11]=[C:10](Br)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:13]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[F-].[Cs+]>CN(C=O)C.O.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:7][O:6][C:4]([C:3]1[CH:8]=[CH:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:11][C:2]=1[F:1])=[O:5]

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 66827Phenylboronic AcidHCID 113453114-Bromo-2-fluoro-benzoic acid methyl ester

Product 1

HCID 69129634Methyl 2-fluoro-4-phenylbenzoate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Combine methyl 2-fluoro-4-bromobenzoate (1.25 g, 5.36 mmol), phenylboronic acid (1.30 g, 10.72 mmol) and CsF (2.02 g, 13.40 mmol) in DMF (25 mL) and water (3.0 mL) with stirring. Place the hetereogeneous reaction mixture open to the air in an oil bath maintained at 80° C. After 5 minutes of heating, add Pd(OAc)2 (120 mg, 0.536 mmol) in one portion and stir until reaction turns black. Cool reaction to room temperature, dilute with ethyl acetate and filter through a short plug of celite with additional ethyl acetate. Wash organics with water, dry over MgSO4, filter and evaporate. Purification by flash column chromatography yields 3-fluorobiphenyl-4-carboxylic acid methyl ester as a solid. Dissolve the purified ester in THF (0.25M) and add an equal volume of 1 M NaOH. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCl and extract with ethyl acetate. Evaporation of the solvent yields 965 mg (84%) of the title compound. MS (m/e): 214.9 (M−).

Workup

  1. temperatureAfter 5 minutes of heating
  2. temperatureCool
  3. customreaction to room temperature
  4. filtrationfilter through a short plug of celite with additional ethyl acetate
  5. dry with materialWash organics with water, dry over MgSO4
  6. filtrationfilter
  7. customevaporate
  8. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-830f2c86c7b341fea80b114671a8c421
Source dataset
uspto-grants-2008_02
Patent number
US07326731B2

Reaction notes

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