3,5-Dichloro-2-cyanopyridine → 5-((4-Acetylphenyl)ethynyl)-3-chloropicolinonitrile

HRID 1479660Notes

Reaction equation

HRID 1479660 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:11])[CH3:10])=[CH:5][CH:4]=1)#[CH:2].[Cl:12][C:13]1[C:14]([C:20]#[N:21])=[N:15][CH:16]=[C:17](Cl)[CH:18]=1.CN(C=O)C.C(N(CC)CC)C>C(OCC)(=O)C.C(=O)(O)[O-].[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[C:9]([C:6]1[CH:7]=[CH:8][C:3]([C:1]#[C:2][C:17]2[CH:18]=[C:13]([Cl:12])[C:14]([C:20]#[N:21])=[N:15][CH:16]=2)=[CH:4][CH:5]=1)(=[O:11])[CH3:10]

Participants

8

Reactant 3

HCID 27696993,5-Dichloro-2-cyanopyridineHCID 51236261-(4-Ethynylphenyl)ethan-1-oneHCID 22056947triethylamine N,N-dimethylformamide

Product 1

HCID 668749115-((4-Acetylphenyl)ethynyl)-3-chloropicolinonitrile

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 1-(4-ethynylphenyl)ethanone (commercially available) (1 eq) 3,5-dichloropicolinonitrile (1 eq), dichlorobis(triphenylphosphine)-palladium (II) (20 mol %), copper iodide (10 mol %) and DMF:Triethylamine (10:1) (0.13 M) was stirred at ambient temperature overnight. The reaction mixture was then diluted with ethyl acetate and sodium bicarbonate solution. The two phases were separated, and the aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-100% ethyl acetate in hexane and 5-((4-acetylphenyl)ethynyl)-3-chloropicolinonitrile was isolated as a yellow solid

Workup

  1. customThe two phases were separated
  2. extractionthe aqueous phase was extracted twice with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated en vaccuo
  6. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  7. customwas isolated as a yellow solid

Sources & evidence

ORD record
ord-1dce481e0e9f462ca13427305d945274
Source dataset
uspto-grants-2016_08
Patent number
US09408907B2

Reaction notes

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