Sodium Hydroxide → 3',4'-Difluoro[1,1'-biphenyl]-4-carboxylic acid
Reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)=[CH:7][CH:6]=1)=[O:4].[OH-].[Na+]>O1CCOCC1>[F:18][C:13]1[CH:12]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([C:3]([OH:4])=[O:2])=[CH:6][CH:7]=2)[CH:16]=[CH:15][C:14]=1[F:17]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
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 (m/e): 235 (M+).
Workup
- customRemove the solvent
- customby evaporation
- dissolutionDissolve the residue in dichloromethane
- washwash with 1N aqueous hydrochloric acid
- dry with materialDry the organics over MgSO4
- filtrationfilter
- customevaporate
Sources & evidence
- ORD record
- ord-1dd1438bccef4428ab4b64faf6095f68
- Source dataset
- uspto-grants-2008_02
- Patent number
- US07326731B2
Reaction notes
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