6-Bromoquinoline → (Quinolin-6-yl)acetonitrile

HRID 1099056Notes

Reaction equation

HRID 1099056 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.C[Si]([CH2:16][C:17]#[N:18])(C)C>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[F-].[F-].[Zn+2].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>[N:8]1[C:9]2[C:4](=[CH:3][C:2]([CH2:16][C:17]#[N:18])=[CH:11][CH:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 2

HCID 792436-BromoquinolineHCID 87557(Trimethylsilyl)acetonitrile

Product 1

HCID 21992552(Quinolin-6-yl)acetonitrileYield 72.1%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 10129912Zinc(II) fluorideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (6.7 g, 0.012 mol), tris(dibenzylideneacetone)dipalladium(0) (10.0 g, 0.012 mol), 6-bromoquinoline (120.0 g, 0.577 mol) in DMF (360 mL) in a 3-neck round bottom flask with stirring under an atmosphere of nitrogen was added (trimethylsilyl)acetonitrile (98.7 mL, 0.721 mol), followed by zinc difluoride (42 g, 0.40 mol). The flask was sealed under an atmosphere of nitrogen. The reaction was stirred at 105° C. for 20 h. After cooling the solution to RT, the reaction mixture was quenched with aqueous ammonia solution and extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (ethyl acetate in hexanes: 0-65%) to afford the desired product quinolin-6-ylacetonitrile (70 g, 72.1%). Analytical LCMS: (M+H)+=168.9.

Workup

  1. customThe flask was sealed under an atmosphere of nitrogen
  2. stirringThe reaction was stirred at 105° C. for 20 h
  3. customthe reaction mixture was quenched with aqueous ammonia solution
  4. extractionextracted with ethyl acetate (3×500 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was chromatographed on a silica gel column (ethyl acetate in hexanes: 0-65%)

Sources & evidence

ORD record
ord-51ed9ee3cb0c4abb86c3caec7c5a6dad
Source dataset
uspto-grants-2012_03
Patent number
US08143251B2

Reaction notes

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