Methyl 4-bromobenzoate → HCID 69129920, compound

HRID 915630Notes

Reaction equation

HRID 915630 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 dimethylformamide (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 magnesium sulfate, 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 1M aqueous sodium hydroxide. 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 magnesium sulfate, filter and evaporate to yield 0.048 g (12%) of the title compound. MS (m/e): 235 (M+).

Workup

  1. customPurge the reaction vessel with argon
  2. additionadd anhydrous dimethylformamide (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 magnesium sulfate
  9. filtrationfilter
  10. customevaporate
  11. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-0dbc549af0104938aef7bae219cc10fb
Source dataset
uspto-grants-2007_09
Patent number
US07265246B2

Reaction notes

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