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

HRID 1877457Notes

Reaction equation

HRID 1877457 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.[CH:59]1[C:71]2[NH:70][C:69]3[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=3)[C:63]=2[C:62]([C:72]2[CH:73]=[CH:74][C:75]([CH2:78][OH:79])=[N:76][CH:77]=2)=[CH:61][CH:60]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:10][C:4]1[CH:3]=[C:2]([N:70]2[C:71]3[CH:59]=[CH:60][CH:61]=[C:62]([C:72]4[CH:77]=[N:76][C:75]([CH2:78][OH:79])=[CH:74][CH:73]=4)[C:63]=3[C:64]3[C:69]2=[CH:68][CH:67]=[CH:66][CH:65]=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 67308755[5-(9H-carbazol-4-yl)pyridin-2-yl]methanol

Product 1

HCID 673071812-fluoro-4-{4-[6-(hydroxymethyl)pyridin-3-yl]-9H-carbazol-9-yl}benzonitrileYield 15.7%

Reagents, catalysts & solvents 2

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

Procedure

0.34 g of 4-bromo-2-fluorobenzonitrile, 1.4 g of caesium carbonate, 0.08 g of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) and 25 mg of palladium acetate are successively added, under argon, to a solution of 0.31 g of [5-(9H-carbazol-4-yl)pyridin-2-yl]methanol in 15 ml of dioxane. The reaction mixture is refluxed for 4 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 (85/15 by volume), so as to give 70 mg of 2-fluoro-4-{4-[6-(hydroxymethyl)pyridin-3-yl]-9H-carbazol-9-yl}benzonitrile in the form of a yellow solid, the characteristics of which are the following:

Workup

  1. temperatureThe reaction mixture is refluxed for 4 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 (85/15 by volume)

Sources & evidence

ORD record
ord-f7f49cf26e254caaa094f568e5c86aeb
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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