2-Chloropyridine-4-carbonyl chloride → 2-(2-Chloro-pyridine-4-carbonyl)-6-fluorobenzonitrile

HRID 1662215Notes

Reaction equation

HRID 1662215 reaction equation
[I-].[C:2]([C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[Zn+])#[N:3].[Cl:12][C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][N:21]=1)[C:16](Cl)=[O:17]>C1COCC1.C(OCC)(=O)C.O.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>[Cl:12][C:13]1[CH:14]=[C:15]([C:16]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([F:10])[C:4]=2[C:2]#[N:3])=[O:17])[CH:19]=[CH:20][N:21]=1

Participants

7

Reactant 2

HCID 28000032-Chloropyridine-4-carbonyl chlorideHCID 178510276HCID 178510276, compound

Product 1

HCID 585795302-(2-Chloro-pyridine-4-carbonyl)-6-fluorobenzonitrileYield 89.1%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-cyano-3-fluorophenylzinc iodide (0.5 M, 31 mL, 15.5 mmol) in THF was added 2-chloro-isonicotinoyl chloride (3 g, 17.05 mmol), followed by Pd(PPh3)2Cl2 (0.33 g, 0.465 mmol). The resulting mixture was stirred at room temperature for 4 hours and diluted with ethyl acetate (80 mL) and H2O (40 mL). The organic phase was separated, washed with H2O (3×30 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using a gradient of 20-50% EtOAc in hexane to afford of the title compound (3.6 g, 88%).

Workup

  1. customThe organic phase was separated
  2. washwashed with H2O (3×30 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-19578cc4cf0a44aa9a523b3521971b3d
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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