3,5-Dichloro-2-cyanopyridine → 3-Chloro-5-methoxypicolinonitrile

HRID 340218

Reaction equation

HRID 340218 reaction equation
[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6](Cl)[CH:7]=1.[CH3:11][O-:12].[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6]([O:12][CH3:11])[CH:7]=1

Participants

6

Reactant 2

HCID 27696993,5-Dichloro-2-cyanopyridineHCID 10942334Sodium Methoxide

Product 1

HCID 187968643-Chloro-5-methoxypicolinonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 3,5-dichloropicolinonitrile (1.0 eq.) in dimethyl formamide (DMF) (0.5 M) was added sodium methoxide (1.5 eq.) and heated to 75° C. After stirring for 14 hours, the reaction was diluted with ethyl acetate and water. The organic layer was washed with saturated aqueous NaHCO3 three times, water twice, dried over anhydrous MgSO4, and concentrated en vacuo. The crude residue was purified by a COMBIFLASH® system (ISCO) using 15% ethyl acetate in hexane to give a mixture of two methoxy regioisomers, one of which was the desired product. The mixture was carried onto the next step without further purification.

Workup

  1. washThe organic layer was washed with saturated aqueous NaHCO3 three times, water twice
  2. dry with materialdried over anhydrous MgSO4
  3. concentrationconcentrated en vacuo
  4. customThe crude residue was purified by a COMBIFLASH® system (ISCO)
  5. customto give
  6. additiona mixture of two methoxy regioisomers, one of which

Sources & evidence

ORD record
ord-644b96ca644b477a93e2eaf644a3f724
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Linked notes

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