Hydrochloric Acid → Tert-butyl 2-(2-fluoroanilino)-4-phenethylbenzoate

HRID 2191841Notes

Reaction equation

HRID 2191841 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1I.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[NH2:43][C:44]1[CH:56]=[C:55]([CH2:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:54]=[CH:53][C:45]=1[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47].C(=O)([O-])[O-].[Cs+].[Cs+].Cl>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.C(OCC)(=O)C.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:43][C:44]1[CH:56]=[C:55]([CH2:57][CH2:58][C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH:54]=[CH:53][C:45]=1[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 676731-Fluoro-2-iodobenzeneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 58508624Tert-butyl 2-amino-4-phenethylbenzoate

Product 1

HCID 68960172Tert-butyl 2-(2-fluoroanilino)-4-phenethylbenzoateYield 79.8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 1-fluoro-2-iodobenzene 0.11 g were added 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 9.5 mg, tris(dibenzylideneacetone)dipalladium(0) 3.7 mg, palladium acetate 0.90 mg, tert-butyl 2-amino-4-phenethylbenzoate 59 mg, cesium carbonate 0.13 g and toluene 1.0 mL at room temperature, and it was heated and refluxed for 9 hours and 30 minutes. After the reaction mixture was cooled to room temperature, 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 washing with 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=200:1] to give tert-butyl 2-(2-fluoroanilino)-4-phenethylbenzoate 62 mg of a colorless oil.

Workup

  1. temperatureit was heated
  2. temperaturerefluxed for 9 hours and 30 minutes
  3. customThe organic layer was separated
  4. customcollected
  5. dry with materialdried over anhydrous magnesium sulfate
  6. washafter washing with saturated sodium chloride aqueous solution
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-43065d0f300641e2b651b9791bcc7ecf
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

Loading…