Citric Acid → HCID 68962723, compound

HRID 2191778Notes

Reaction equation

HRID 2191778 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[C:4]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:3]=1.[N+:23]([C:26]1[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=1[NH2:28])([O-:25])=[O:24].C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(OCC)(=O)C.C1(C)C=CC=CC=1>[F:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:4]2[CH:3]=[C:2]([NH:28][C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[N+:23]([O-:25])=[O:24])[CH:14]=[CH:13][C:5]=2[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:17][CH:18]=1

Participants

10

Reactant 4

HCID 311Citric AcidHCID 69462-NitroanilineHCID 10796Cesium carbonateHCID 68956988Tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate

Product 1

HCID 68962723HCID 68962723, compoundYield 100.9%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalyst3×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst3×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst3×HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To toluene 3.0 mL solution of tert-butyl 4-bromo-2-(4-fluoroanilino)benzoate 0.30 g were added 2-nitroaniline 0.17 g, cesium carbonate 0.53 g, tris(dibenzylideneacetone)dipalladium(0) 8.0 mg, palladium acetate 4.0 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 20 mg at room temperature, and it was heated and refluxed under nitrogen atmosphere for 2 hours. Tris(dibenzylideneacetone)dipalladium(0) 8.0 mg, palladium acetate 4.0 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 20 mg were added to it, and it was heated and refluxed for 3 hours. Tris(dibenzylideneacetone)dipalladium(0) 8.0 mg, palladium acetate 4.0 mg and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 20 mg were added to it, and it was heated and refluxed for 7 hours. After the reaction mixture was cooled to room temperature, toluene, ethyl acetate and 10% citric acid aqueous solution were added to it, and 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, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=10:1] to give tert-butyl 2-(4-fluoroanilino)-4-(2-nitroanilino)benzoate 0.35 g of a yellow solid.

Workup

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

Sources & evidence

ORD record
ord-ea5cfcbe5c0845ea85532b3fb40d5799
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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