Cesium carbonate → 2-fluoro-4-{4-[6-(trifluoromethyl)pyridin-3-yl]-9H-carbazol-9-yl}benzonitrile

HRID 1877481Notes

Reaction equation

HRID 1877481 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([F:10])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[F:59][C:60]([F:81])([F:80])[C:61]1[N:66]=[CH:65][C:64]([C:67]2[C:79]3[C:78]4[C:73](=[CH:74][CH:75]=[CH:76][CH:77]=4)[NH:72][C:71]=3[CH:70]=[CH:69][CH:68]=2)=[CH:63][CH:62]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:10][C:4]1[CH:3]=[C:2]([N:72]2[C:71]3[CH:70]=[CH:69][CH:68]=[C:67]([C:64]4[CH:65]=[N:66][C:61]([C:60]([F:81])([F:59])[F:80])=[CH:62][CH:63]=4)[C:79]=3[C:78]3[C:73]2=[CH:74][CH:75]=[CH:76][CH:77]=3)[CH:9]=[CH:8][C:5]=1[C:6]#[N:7]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7360294-Bromo-2-fluorobenzonitrileHCID 673081124-[6-(trifluoromethyl)pyridin-3-yl]-9H-carbazole

Product 1

HCID 673087102-fluoro-4-{4-[6-(trifluoromethyl)pyridin-3-yl]-9H-carbazol-9-yl}benzonitrileYield 49.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

0.52 g of 4-bromo-2-fluorobenzonitrile, 2.14 g of caesium carbonate, 0.12 g of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) and 39 mg of palladium acetate are successively added, under argon, to a solution of 0.54 g of 4-[6-(trifluoromethyl)pyridin-3-yl]-9H-carbazole in 50 ml of dioxane. The reaction mixture is refluxed for 6 hours, cooled to ambient temperature, filtered through celite and concentrated under reduced pressure. The residue is purified by silica gel chromatography, elution being carried out with a mixture of cyclohexane and ethyl acetate (96/4 by volume) so as to give 0.37 g of 2-fluoro-4-{4-[6-(trifluoro-methyl)pyridin-3-yl]-9H-carbazol-9-yl}benzonitrile in the form of a white powder, the characteristics of which are the following:

Workup

  1. temperatureThe reaction mixture is refluxed for 6 hours
  2. filtrationfiltered through celite and
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by silica gel chromatography, elution
  5. additionbeing carried out with a mixture of cyclohexane and ethyl acetate (96/4 by volume) so as

Sources & evidence

ORD record
ord-4ef2e143359a4232988da61024431f5a
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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