4-Bromoaniline → 4'-Trifluoromethoxy-biphenyl-4-ylamine

HRID 855995Notes

Reaction equation

HRID 855995 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1.Br[C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:16]2[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=2)=[CH:6][CH:5]=1

Participants

8

Reactant 3

HCID 78074-BromoanilineHCID 11430Potassium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acid

Product 1

HCID 27607274'-Trifluoromethoxy-biphenyl-4-ylamineYield 48%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-trifluoromethoxylbenzeneboronic acid (300 mg, 1.45 mmol), p-bromoaniline (100 mg, 0.58 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (24 mg,0.029 mmol), 1,1′-bis(diphenylphosphino)ferrocene (16 mg, 0.029 mmol) and potassium carbonate (0.58 ml of a 2M aqueous solution, 1.16 mmol) in 5 ml 1,4-dioxane was heated at reflux under nitrogen for 20 hr. The reaction mixture was cooled to room temperature, diluted with 40 ml water and extracted with 2×40 ml ethyl acetate. The combined ethyl acetate extracts were washed with 40 ml brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel, 15 g), eluting with 10:1 hexane/ethyl acetate to yield the title compound as a tan solid (70 mg, 48% yield). MS: 254.1 (M+1)

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 20 hr
  3. extractionextracted with 2×40 ml ethyl acetate
  4. washThe combined ethyl acetate extracts were washed with 40 ml brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by flash column chromatography (silica gel, 15 g)
  8. washeluting with 10:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-d8f34f1d9120485e8e0e4696d3c8fe77
Source dataset
uspto-grants-2007_08
Patent number
US07262318B2

Reaction notes

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