Potassium Cyanide → 2-(2,6-Dichloropyridin-3-yl)acetonitrile

HRID 2197499Notes

Reaction equation

HRID 2197499 reaction equation
[C-]#N.[K+].Br[CH2:5][C:6]1[C:7]([Cl:13])=[N:8][C:9]([Cl:12])=[CH:10][CH:11]=1.BrCC1(CBr)C=CC(Cl)=[N:18][CH:17]1Cl>O.C(O)C>[Cl:13][C:7]1[C:6]([CH2:5][C:17]#[N:18])=[CH:11][CH:10]=[C:9]([Cl:12])[N:8]=1

Participants

6

Reactant 3

HCID 9032Potassium Cyanide2×HCID 122653943-(Bromomethyl)-2,6-dichloropyridine2×HCID 668505573,3-Dibromomethyl-2,6-dichloro-pyridine

Product 1

HCID 122653992-(2,6-Dichloropyridin-3-yl)acetonitrile

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

Potassium cyanide (1.0 g) was dissolved in water by heating to 40° C. A mixture of 3-bromomethyl-2,6-dichloro-pyridine, 3,3-dibromomethyl-2,6-dichloro-pyridine, and 2,6-dichloro-3-methyl-pyridine (Example 4.1) (3.2 g) suspended in ethanol (20 ml) was added dropwise at 40° C. over a period of 30 minutes. The reaction mixture was heated to reflux for 3 hours. The reaction mixture was cooled to 40° C. and another equivalent of potassium cyanide was added. The reaction mixture was heated to reflux for a further 3 hours and then stored at ambient temperature for 16 hours. The reaction mixture was filtered to remove the solids and the solids were washed with ethyl acetate. The combined filtrates were concentrated. The residue was diluted with ethyl acetate. The organic solution washed with aqueous sodium hydrogen carbonate (saturated) and brine, dried over magnesium sulfate, and concentrated. This residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane from 3:100 to 1:1) to give slightly impure (2,6-dichloro-pyrid-3-yl)-acetonitrile (1.5 g) which solidified on standing. This material was used without further purification. 1H-NMR (400 MHz, CDCl3): 3.83 (s, 2H), 7.37 (d, 1H), 7.85 (d, 1H) ppm.

Workup

  1. additionwas added dropwise at 40° C. over a period of 30 minutes
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 3 hours
  4. temperatureThe reaction mixture was cooled to 40° C.
  5. temperatureThe reaction mixture was heated
  6. temperatureto reflux for a further 3 hours
  7. filtrationThe reaction mixture was filtered
  8. customto remove the solids
  9. washthe solids were washed with ethyl acetate
  10. concentrationThe combined filtrates were concentrated
  11. additionThe residue was diluted with ethyl acetate
  12. washThe organic solution washed with aqueous sodium hydrogen carbonate (saturated) and brine
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated
  15. customThis residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane from 3:100 to 1:1)

Sources & evidence

ORD record
ord-e8fc3857834941afb926f205ec4e596d
Source dataset
uspto-grants-2012_12
Patent number
US08338598B2

Reaction notes

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