Sodium Carbonate → HCID 57667972, compound

HRID 2191646Notes

Reaction equation

HRID 2191646 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.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>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]([O:21][CH3:20])=[CH:23][CH:24]=3)[CH:11]=[CH:10][C:5]=2[C:6]([OH:8])=[O:7])=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 57667801HCID 57667801, compound

Product 1

HCID 57667972HCID 57667972, compoundYield 26.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
160 °C

Procedure

To N,N-dimethylacetamide 3.0 mL solution of methyl 4-bromo-2-(4-fluoroanilino)benzoate 70 mg were added 4-methoxyphenylboronic acid 66 mg, sodium carbonate 69 mg and polymer-carried bis(acetato)triphenylphosphine palladium(II) 31 mg at room temperature, and it was stirred under application of pressure at 160° C. for 5 minutes. After the reaction mixture was cooled to room temperature, it was stirred under application of pressure at 180° C. for 5 minutes. After the reaction mixture was cooled to room temperature, it was stirred under application of pressure at 200° C. for 5 minutes. After the reaction mixture was cooled to room temperature, it was stirred under application of pressure at 220° C. for 5 minutes. After the reaction mixture was cooled to room temperature, insoluble matter was filtrated, and ethyl acetate and 0.5 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 4.0 mL were added to the obtained residue, and it was stirred at room temperature for 1 hour and 30 minutes. 0.7 mol/L hydrochloric acid and ethyl acetate 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; 50-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to give 2-(4-fluoroanilino)-4-(4-methoxyphenyl)benzoic acid 19 mg of pale yellow solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringit was stirred under application of pressure at 180° C. for 5 minutes
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. stirringit was stirred under application of pressure at 200° C. for 5 minutes
  5. temperatureAfter the reaction mixture was cooled to room temperature
  6. stirringit was stirred under application of pressure at 220° C. for 5 minutes
  7. temperatureAfter the reaction mixture was cooled to room temperature
  8. filtrationinsoluble matter was filtrated
  9. additionethyl acetate and 0.5 mol/L hydrochloric acid were added to it
  10. customThe organic layer was separated
  11. customcollected
  12. dry with materialdried over anhydrous magnesium sulfate
  13. washafter sequential washing with 1.0 mol/L hydrochloric acid and saturated sodium chloride aqueous solution
  14. customthe solvent was removed under reduced pressure
  15. addition2.0 mol/L sodium hydroxide aqueous solution 1.0 mL and ethanol 4.0 mL were added to the obtained residue, and it
  16. stirringwas stirred at room temperature for 1 hour and 30 minutes
  17. addition0.7 mol/L hydrochloric acid and ethyl acetate were added to the reaction mixture
  18. customthe organic layer was separated
  19. customcollected
  20. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-66cc7835a6e64859be086b9d4115a0b1
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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