Dimethylformamide → 5-Chloro-2-cyanopyridine

HRID 911302Notes

Reaction equation

HRID 911302 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.[CH3:9][N:10](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.[Zn]>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:9]#[N:10])=[N:3][CH:4]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 276852,5-Dichloropyridine

Product 1

HCID 38339425-Chloro-2-cyanopyridineYield 46%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Add 2,5-dichloropyridine (6.0 g, 40.5 mmol), zinc cyanide (2.9 g, 24.7 mmol), zinc dust (16 mg, 1.8 mmol) and 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (20 mg, 0.98 mmol) to a flask containing DMF (40 mL). Heat the mixture to reflux for 5 h, then cool to ambient temperature. Dilute the mixture with EtOAc (300 mL) and wash with 10% aqueous NaCl (3×75 mL). Collect the organic layer, concentrate in vacuo and purify by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1) to obtain the desired intermediate (2.6 g, 46%).

Workup

  1. temperatureHeat the mixture
  2. temperatureto reflux for 5 h
  3. washwash with 10% aqueous NaCl (3×75 mL)
  4. customCollect the organic layer
  5. concentrationconcentrate in vacuo
  6. custompurify by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1)

Sources & evidence

ORD record
ord-5d86c538c2634f8b941880c7464a87a3
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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