Potassium Carbonate → 6-(((3-Bromo-4-(trifluoromethoxy)phenyl)amino)methyl)benzofuran-2-carbonitrile

HRID 1773235Notes

Reaction equation

HRID 1773235 reaction equation
Br[CH2:2][C:3]1[CH:13]=[CH:12][C:6]2[CH:7]=[C:8]([C:10]#[N:11])[O:9][C:5]=2[CH:4]=1.C([O-])([O-])=O.[K+].[K+].[Br:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[O:28][C:29]([F:32])([F:31])[F:30])[NH2:24]>CN(C=O)C.CCOC(C)=O.O>[Br:20][C:21]1[CH:22]=[C:23]([NH:24][CH2:2][C:3]2[CH:13]=[CH:12][C:6]3[CH:7]=[C:8]([C:10]#[N:11])[O:9][C:5]=3[CH:4]=2)[CH:25]=[CH:26][C:27]=1[O:28][C:29]([F:31])([F:32])[F:30]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27364183-Bromo-4-(trifluoromethoxy)anilineHCID 1184524986-(Bromomethyl)benzofuran-2-carbonitrile

Product 1

HCID 1184525066-(((3-Bromo-4-(trifluoromethoxy)phenyl)amino)methyl)benzofuran-2-carbonitrileYield 74.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-(bromomethyl)benzofuran-2-carbonitrile (0.5 g, 2.12 mmol) was dissolved in DMF (21.2 ml). K2CO3 (0.44 g, 3.18 mmol) was added, followed by 3-bromo-4-(trifluoromethoxy)aniline (314 μL, 2.12 mmol), and the mixture was stirred at RT for 18 hr. The reaction was diluted with EtOAc and water. The organic layer was washed with water×6, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude mixture was diluted with DCM and silica gel was added. The mixture was concentrated under reduced pressure to dry-load material for purification. The crude mixture was purified via silica gel FCC, 100% Heptane-50% EtOAc/50% Heptane to give 6-(((3-bromo-4-(trifluoromethoxy)phenyl)amino)methyl)benzofuran-2-carbonitrile (651 mg). LCMS retention time=1.57 minutes (LC method 1); MS (m+1)=412.1. 1H NMR (400 MHz, DMSO-d6) δ 4.46 (d, J=6.0 Hz, 2H), 6.62 (dd, J=9.0, 2.8 Hz, 1H), 6.88-6.95 (m, 2H), 7.17 (dq, J=9.0, 1.3 Hz, 1H), 7.44 (dd, J=8.2, 1.4 Hz, 1H), 7.70 (s, 1H), 7.80 (dd, J=8.1, 0.7 Hz, 1H), 8.08 (d, J=1.0 Hz, 1H).

Workup

  1. washThe organic layer was washed with water×6, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. additionThe crude mixture was diluted with DCM and silica gel
  6. additionwas added
  7. concentrationThe mixture was concentrated under reduced pressure
  8. customto dry-load material
  9. customfor purification
  10. customThe crude mixture was purified via silica gel FCC, 100% Heptane-50% EtOAc/50% Heptane

Sources & evidence

ORD record
ord-1ffb6efce8f649de9f82e0f9de98e9c1
Source dataset
uspto-grants-2016_02
Patent number
US09255093B2

Reaction notes

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