Sodium Cyanide → 2-Methylquinoline-8-carbonitrile

HRID 338891Notes

Reaction equation

HRID 338891 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[C:14]([CH3:17])[CH:13]=[CH:12]2)(=O)=O.[C-:20]#[N:21].[Na+]>C(#N)C.C(OCC)(=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:17][C:14]1[CH:13]=[CH:12][C:11]2[C:16](=[C:7]([C:20]#[N:21])[CH:8]=[CH:9][CH:10]=2)[N:15]=1

Participants

7

Reactant 2

HCID 8929Sodium CyanideHCID 15424298HCID 15424298, compound

Product 1

HCID 336982272-Methylquinoline-8-carbonitrileYield 98.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-methylquinolin-8-yl trifluoromethanesulfonate (3.0 g, 10.3 mmol) in acetonitrile (26 mL) was added sodium cyanide (1.0 g, 20.6 mmol). The solution was degassed under nitrogen for 10 minutes, followed by addition of copper (I) iodide (0.20 g, 1.03 mmol) and Pd(PPh3)4 (0.60 g, 0.52 mmol) under nitrogen. The mixture was heated at reflux for 2 hours. After cooling the mixture was diluted with ethyl acetate (50 mL) and filtered through Celite and washed with ethyl acetate (50 mL). The filtrate was washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage, 40 M; 20% ethyl acetate:hexanes) to afford 2-methylquinoline-8-carbonitrile (1.70 g, 98%).

Workup

  1. customThe solution was degassed under nitrogen for 10 minutes
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 2 hours
  4. temperatureAfter cooling the mixture
  5. filtrationfiltered through Celite
  6. washwashed with ethyl acetate (50 mL)
  7. washThe filtrate was washed with water and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography (Biotage, 40 M; 20% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-d87090d9f53c43cbabca6226ddf54996
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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