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

HRID 1526543Notes

Reaction equation

HRID 1526543 reaction equation
[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:11][O-:12].[Na+]>CN(C=O)C>[Cl:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6]([O:12][CH3:11])[CH:7]=1.[Cl:8][C:6]1[CH:7]=[C:2]([O:12][CH3:11])[C:3]([C:9]#[N:10])=[N:4][CH:5]=1

Participants

5

Reactant 2

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

Product 2

HCID 187968643-Chloro-5-methoxypicolinonitrileHCID 735549095-Chloro-3-methoxypicolinonitrileYield 66.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3,5-dichloropicolinonitrile (22.5 g, 130 mmol) in DMF (500 mL) at 0° C. was added sodium methoxide (6.67 g, 124 mmol) slowly. The reaction was stirred for 5 minutes at 0° C., then it was allowed to warm to RT and stir for 30 minutes. The solution was partitioned between water and EtOAc. The organic layer was washed with water and concentrated. The crude product was purified via silica gel chromatography, eluting with 0-75% ethyl acetate in heptanes, to afford a 1:1 ratio of the desired isomer 3-chloro-5-methoxypicolinonitrile and 5-chloro-3-methoxypicolinonitrile (7.0 g, 41.5 mmol). The material was used without further purification. MS m/z=169 (M+H).

Workup

  1. temperatureto warm to RT
  2. stirringstir for 30 minutes
  3. customThe solution was partitioned between water and EtOAc
  4. washThe organic layer was washed with water
  5. concentrationconcentrated
  6. customThe crude product was purified via silica gel chromatography
  7. washeluting with 0-75% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-65032bbc2abe40d7b2c3925cf825ca7c
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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