Dimethylformamide → 5-Chloro-2-cyanopyridine

HRID 911637Notes

Reaction equation

HRID 911637 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.ClCCl.[CH3:12][N:13](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:12]#[N:13])=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 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

Slurry 2,5-dichloropyridine (6 g, 40.5 mmol), zinc cyanide (2.9 g, 24.7 mmol), zinc (dust) (116 mg, 1.8 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (720 mg, 0.98 mmol) in anhydrous DMF (40 mL). Heat the mixture to reflux under a nitrogen atmosphere for 4.5 h. Cool the mixture to room temperature, dilute with EtOAc (300 mL), wash with aqueous 10% sodium chloride (3×75 mL). Collect organic layer, dry over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1 gradient) to obtain the desired intermediate (2.6 g, 46%). GC-MS m/z: 138 (M+).

Workup

  1. temperatureHeat the mixture
  2. temperatureto reflux under a nitrogen atmosphere for 4.5 h
  3. washwash with aqueous 10% sodium chloride (3×75 mL)
  4. dry with materialCollect organic layer, dry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1 gradient)

Sources & evidence

ORD record
ord-ba30d6e103e04a4b896ab3610c17387f
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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