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

HRID 1257806Notes

Reaction equation

HRID 1257806 reaction equation
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.Br[C:44]1[CH:45]=[C:46]2[C:51](=[CH:52][CH:53]=1)[N:50]=[CH:49][CH:48]=[CH:47]2.C[Si]([CH2:58][C:59]#[N:60])(C)C>CN(C)C=O.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]>[N:50]1[C:51]2[C:46](=[CH:45][C:44]([CH2:58][C:59]#[N:60])=[CH:53][CH:52]=2)[CH:47]=[CH:48][CH:49]=1

Participants

7

Reactant 3

HCID 792436-BromoquinolineHCID 87557(Trimethylsilyl)acetonitrileHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 21992552(Quinolin-6-yl)acetonitrile

Reagents, catalysts & solvents 3

HCID 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, 12 mmol), tris(dibenzylideneacetone)dipalladium(0) (10 g, 12 mmol), 6-bromoquinoline (120 g, 577 mmol) in N,N-dimethylformamide (360 mL) in a 3-neck round bottom flask with stirring under positive nitrogen pressure was added (trimethylsilyl)acetonitrile (98.7 mL, 721 mmol), followed by zinc difluoride (42 g, 400 mmol). The flask was sealed under an atmosphere of nitrogen. The reaction mixture was stirred at 105° C. for 20 h. After cooling the solution to RT, the reaction mixture was quenched with an aqueous ammonia solution and extracted with ethyl acetate (3×500 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified under flash chromatography eluting with ethyl acetate in hexanes (0-65%) to afford the desired product. (70 g, 72.1%) LCMS: (M+H)=168.9.

Workup

  1. customThe flask was sealed under an atmosphere of nitrogen
  2. stirringThe reaction mixture was stirred at 105° C. for 20 h
  3. customthe reaction mixture was quenched with an aqueous ammonia solution
  4. extractionextracted with ethyl acetate (3×500 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified under flash chromatography
  10. washeluting with ethyl acetate in hexanes (0-65%)

Sources & evidence

ORD record
ord-5c070b4484464294b9ef36f56d25884b
Source dataset
uspto-grants-2013_06
Patent number
US08461330B2

Reaction notes

Loading…