Hydrochloric Acid → 5-(Chloromethyl)pyridine-3-carbonitrile

HRID 45239Notes

Reaction equation

HRID 45239 reaction equation
O[CH2:2][C:3]1[CH:4]=[C:5]([C:9]#[N:10])[CH:6]=[N:7][CH:8]=1.Cl.S(Cl)([Cl:14])=O>C(Cl)Cl.O1CCOCC1.C1(C)C=CC=CC=1>[Cl:14][CH2:2][C:3]1[CH:4]=[C:5]([C:9]#[N:10])[CH:6]=[N:7][CH:8]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 224165405-(Hydroxymethyl)nicotinonitrile

Product 1

HCID 221467115-(Chloromethyl)pyridine-3-carbonitrileYield 73%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To 0.2 g (1.49 mmol) of 5-(hydroxymethyl)pyridine-3-carbonitrile in 2 mL of DCM is added 1 mL (4 mmol) of HCl 4N in dioxane. The mixture is concentrated under reduced pressure and then added to 0.65 mL (8.95 mmol) of thionyl chloride followed by heating for 3 hours at 60° C. After cooling to room temperature, the medium is taken up in 20 mL of toluene, and the precipitate formed is filtered off and then treated with 30 mL of DCM and 30 mL of saturated NaHCO3 solution. The organic phase is separated out and dried over Na2SO4 and then concentrated under reduced pressure. 161 mg of 5-(chloromethyl)pyridine-3-carbonitrile are obtained in the form of an oil.

Workup

  1. concentrationThe mixture is concentrated under reduced pressure
  2. temperatureAfter cooling to room temperature
  3. customthe precipitate formed
  4. filtrationis filtered off
  5. additiontreated with 30 mL of DCM and 30 mL of saturated NaHCO3 solution
  6. customThe organic phase is separated out
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-37f5b4211c5b44b7a55b815ae1fc5d17
Source dataset
uspto-grants-2013_09
Patent number
US08541455B2

Reaction notes

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