Sodium Carbonate → Methyl 4-(2,4-difluorophenyl)benzoate

HRID 2224724Notes

Reaction equation

HRID 2224724 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1)([O:3][CH3:4])=[O:2].Br[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[F:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:4][O:3][C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])=[CH:7][CH:6]=1)=[O:2]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 676741-Bromo-2,4-difluorobenzeneHCID 27343694-Methoxycarbonylphenylboronic acid

Product 1

HCID 57771752Methyl 4-(2,4-difluorophenyl)benzoate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Combine 4-carbomethoxyphenylboronic acid (1.021 g, 5.67 mmol), 1-bromo-2,4-difluorobenzene (1.000 g, 5.181 mmol.), Pd(OAc)2 (0.113 g, 0.50 mmol), triphenylphosphine (0.149 g, 0.505 mmol), and sodium carbonate (1.664 g, 0.568 mmol). Purge the reaction vessel with argon. Add DMF (20 mL) and water (2.0 mL) with stirring. Place sealed reaction in an 80° C. oil bath and allow to stir for 24 hours. 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 2′,4′-difluorobiphenyl-4-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in dioxane (5 mL) and add 5M NaOH (1 mL). Stir vigorously at 50° C. for 15 hours. Upon completion, acidify the reaction with conc. HCl and extract with ethyl acetate. Evaporation of the solvent yields 300 mg (24.7%) of the title compound. MS (ES): m/z 233.0 (M−H).

Workup

  1. customPurge the reaction vessel with argon
  2. customPlace sealed
  3. customreaction in an 80° C. oil bath
  4. stirringto stir for 24 hours
  5. temperatureCool
  6. customreaction to room temperature
  7. filtrationfilter through a short plug of celite with additional ethyl acetate
  8. dry with materialWash organics with water, dry over MgSO4
  9. filtrationfilter
  10. customevaporate
  11. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-91b21a8ea35240a4b56c3e110e8a2558
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

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