Sodium Carbonate → HCID 68963377, compound

HRID 2191759Notes

Reaction equation

HRID 2191759 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.[C:20]([NH:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)(=[O:22])[CH3:21].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C(=O)C>[C:20]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[C:4]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH:3]=2)=[CH:26][CH:25]=1)(=[O:22])[CH3:21]

Participants

5

Reactant 3

HCID 10340Sodium Carbonate2×HCID 27346574-Acetamidophenylboronic acid2×HCID 57667801HCID 57667801, compound

Product 1

HCID 68963377HCID 68963377, compoundYield 17.8%

Reagents, catalysts & solvents 1

HCID 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-(acetamido)phenylboronic acid 77 mg, sodium carbonate 69 mg and polymer-carried di(acetato)dicyclohexylphenylphosphine palladium(II) 31 mg, and it was stirred at 90° C. for 12 hours. After the reaction mixture was cooled to room temperature, 4-(acetamido)phenylboronic acid 39 mg and sodium carbonate 22 mg were added, and it was stirred at 95° C. for 14 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. Ethanol 2.0 mL and 2.0 mol/L sodium hydroxide aqueous solution 1.0 mL were added to the obtained residue, and it was stirred at room temperature for 1 hour. 6.0 mol/L hydrochloric acid 0.50 mL, water 3.0 mL and ethyl acetate 4.0 mL were added to the reaction mixture. The organic layer was separated and collected, and the solvent was removed under reduced pressure. The obtained residue was refined by reversed-phase silica gel column chromatography [eluent; 40-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to give 4-(4-(acetamido)phenyl)-2-(4-fluoroanilino)benzoic acid 14 mg of a pale yellow solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringit was stirred at 95° C. for 14 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. filtrationinsoluble matter was filtrated
  5. additionethyl acetate and 1.0 mol/L hydrochloric acid were added to it
  6. customThe organic layer was separated
  7. customcollected
  8. dry with materialdried over anhydrous magnesium sulfate
  9. washafter sequential washing with 1.0 mol/L hydrochloric acid and saturated sodium chloride aqueous solution
  10. customthe solvent was removed under reduced pressure
  11. additionEthanol 2.0 mL and 2.0 mol/L sodium hydroxide aqueous solution 1.0 mL were added to the obtained residue, and it
  12. stirringwas stirred at room temperature for 1 hour
  13. addition6.0 mol/L hydrochloric acid 0.50 mL, water 3.0 mL and ethyl acetate 4.0 mL were added to the reaction mixture
  14. customThe organic layer was separated
  15. customcollected
  16. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-5aa5bba44ff6492ba984924e87ea5190
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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