Methyl 4-bromobenzoate → HCID 69129920, compound

HRID 2224720Notes

Reaction equation

HRID 2224720 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:12][O:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18](Br)=[CH:17][CH:16]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:12][O:13][C:14]([C:15]1[CH:20]=[CH:19][C:18]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=2)=[CH:17][CH:16]=1)=[O:22]

Participants

7

Reactant 3

HCID 12081Methyl 4-bromobenzoateHCID 62657Potassium Phosphate, TribasicHCID 27343373,4-Difluorobenzeneboronic acid

Product 1

HCID 69129920HCID 69129920, compound

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Combine 3,4-difluorobenzeneboronic acid (1.0 g, 5.2 mmol), methyl-4-bromobenzoate (0.241 g, 1.73 mmol), Pd(OAc)2 (0.019 g, 0.086 mmol), tetrabutylammonium bromide (0.111 g, 0.345 mmol), and potassium phosphate (0.733 g, 3.454 mmol). Purge the reaction vessel with argon and add anhydrous DMF (20 mL) to the reaction mixture. Heat the sealed reaction vessel to 120° C. with stirring until completion. Cool the 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′,4′-difluorobiphenyl-4-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in dioxane (45 mL) and add an equal volume of 1 M aqueous NaOH. Heat the reaction vessel to 60° C. with stirring until completion. Remove the solvent by evaporation. Dissolve the residue in dichloromethane and wash with 1N aqueous hydrochloric acid. Dry the organics over MgSO4, filter and evaporate to yield 0.048 g (12%) of the title compound. MS (ES): m/z 235 (M+H).

Workup

  1. customPurge the reaction vessel with argon
  2. additionadd anhydrous DMF (20 mL) to the reaction mixture
  3. temperatureHeat
  4. customthe sealed reaction vessel to 120° C.
  5. temperatureCool
  6. customthe reaction 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-fb95d181b1b8487ca0b628fe8e3d46c2
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

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