Toluene → Tert-butyl 2-(4-fluoroanilino)-4-phenethylbenzoate

HRID 2191668Notes

Reaction equation

HRID 2191668 reaction equation
C1(C)C=CC=CC=1.[NH2:8][C:9]1[CH:21]=[C:20]([CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:19]=[CH:18][C:10]=1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[F:30][C:31]1[CH:36]=[CH:35][C:34](I)=[CH:33][CH:32]=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>[F:30][C:31]1[CH:36]=[CH:35][C:34]([NH:8][C:9]2[CH:21]=[C:20]([CH2:22][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:19]=[CH:18][C:10]=2[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:33][CH:32]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 96054-FluoroiodobenzeneHCID 10796Cesium carbonateHCID 58508624Tert-butyl 2-amino-4-phenethylbenzoate

Product 1

HCID 68959395Tert-butyl 2-(4-fluoroanilino)-4-phenethylbenzoate

Reagents, catalysts & solvents 3

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

Procedure

To toluene 10 mL solution of tert-butyl 2-amino-4-phenethylbenzoate 1.0 g were added 1-fluoro-4-iodobenzene 0.98 mL, cesium carbonate 2.2 g, palladium acetate 8 mg and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl 21 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 21 mg were added, and it was heated and refluxed under nitrogen atmosphere for 10 hours. After the reaction mixture was cooled to room temperature, water was added to it, and insoluble matter was filtrated. The organic layer was separated and collected,dried over anhydrous magnesium sulfate after sequential washing with saturated sodium hydrogen carbonate 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 [eluent; hexane:ethyl acetate=5:1] to give tert-butyl 2-(4-fluoroanilino)-4-phenethylbenzoate 0.80 g of pale yellow oil.

Workup

  1. temperatureit was heated
  2. temperaturerefluxed under nitrogen atmosphere for 6 hours
  3. temperatureit was heated
  4. temperaturerefluxed under nitrogen atmosphere for 10 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 saturated sodium hydrogen carbonate aqueous solution and saturated sodium chloride aqueous solution
  9. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-f17fcb88faab49ffb22efad70cfa4ae0
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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