Sodium Carbonate → HCID 57668083, compound

HRID 2191645Notes

Reaction equation

HRID 2191645 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH:3]=1.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C)C(=O)C>[F:19][C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:4]2[CH:3]=[C:2]([C:25]3[CH:26]=[CH:27][C:22]([C:21]([F:32])([F:31])[F:20])=[CH:23][CH:24]=3)[CH:11]=[CH:10][C:5]=2[C:6]([OH:8])=[O:7])=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 57667801HCID 57667801, compound

Product 1

HCID 57668083HCID 57668083, compoundYield 22.2%

Reagents, catalysts & solvents 2

HCID 21584511triphenylphosphine palladium (II)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

To N,N-dimethylacetamide 2.5 mL solution of methyl 4-bromo-2-(4-fluoroanilino)benzoate 70 mg were added 4-(trifluoromethyl)phenylboronic acid 62 mg, sodium carbonate 57 mg and polymer-carried bis(acetato) triphenylphosphine palladium (II) 31 mg at room temperature, and it was stirred at 90° C. for 12 hours. After the reaction mixture was cooled to room temperature, insoluble matter was filtrated, and ethyl acetate and 1.0 mol/L hydrochloric acid were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with 1.0 mol/L hydrochloric acid and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. 2.0 mol/L Sodium hydroxide aqueous solution 1.0 mL and ethanol 6.0 mL were added to the obtained residue, and it was stirred at room temperature for 1 hour. 0.5 mol/L Hydrochloric acid was added to the reaction mixture. Solid matter was filtrated, it was refined by reversed-phase silica gel column chromatography [eluent; 50-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to give 2-(4-fluoroanilino)-4-(4-(trifluoromethyl)phenyl)benzoic acid 18 mg of pale yellow solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. filtrationinsoluble matter was filtrated
  3. additionethyl acetate and 1.0 mol/L hydrochloric acid were added to it
  4. customThe organic layer was separated
  5. customcollected
  6. dry with materialdried over anhydrous magnesium sulfate
  7. washafter sequential washing with 1.0 mol/L hydrochloric acid and saturated sodium chloride aqueous solution
  8. customthe solvent was removed under reduced pressure
  9. addition2.0 mol/L Sodium hydroxide aqueous solution 1.0 mL and ethanol 6.0 mL were added to the obtained residue, and it
  10. stirringwas stirred at room temperature for 1 hour
  11. addition0.5 mol/L Hydrochloric acid was added to the reaction mixture
  12. filtrationSolid matter was filtrated

Sources & evidence

ORD record
ord-ab442bdd74764ee2b5a9e9957cedf6d4
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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