Toluene → Tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate

HRID 2191617Notes

Reaction equation

HRID 2191617 reaction equation
C1(C)C=CC=CC=1.[NH2:8][C:9]1[CH:21]=[C:20]([Br:22])[CH:19]=[CH:18][C:10]=1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[F:23][C:24]1[CH:29]=[CH:28][C:27](I)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[Br:22][C:20]1[CH:19]=[CH:18][C:10]([C:11]([O:13][C:14]([CH3:17])([CH3:15])[CH3:16])=[O:12])=[C:9]([NH:8][C:27]2[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=2)[CH:21]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 96054-FluoroiodobenzeneHCID 10796Cesium carbonateHCID 58508534Tert-butyl 2-amino-4-bromobenzoate

Product 1

HCID 68956988Tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 634876Binap, (A+-)-Catalyst2×HCID 962WaterSolvent

Procedure

To toluene 15 mL solution of tert-butyl 2-amino-4-bromobenzoate 1.0 g were added 1-fluoro-4-iodobenzene 0.85 mL, cesium carbonate 3.6 g, palladium acetate 8 mg and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl 23 mg at room temperature, and it was heated and refluxed under nitrogen atmosphere for 6 hours. After the reaction mixture was cooled to room temperature, palladium acetate 8 mg and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl 23 mg were added to it, it was heated and refluxed under nitrogen atmosphere for 8 hours. After the reaction mixture was cooled to room temperature, water was added to it, insoluble matter was filtrated. The organic layer was separated and collected,dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution, the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [eluent; hexane:ethyl acetate=20:1] to give tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate 0.55 g of pale yellow oil.

Workup

  1. temperatureit was heated
  2. temperaturerefluxed under nitrogen atmosphere for 6 hours
  3. temperaturewas heated
  4. temperaturerefluxed under nitrogen atmosphere for 8 hours
  5. temperatureAfter the reaction mixture was cooled to room temperature
  6. filtrationwas filtrated
  7. customThe organic layer was separated
  8. washafter sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution
  9. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c88aac186bd54c2299dbe0853ebdf270
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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