Methanol → 5-(3-Chlorophenyl)-3-methoxy-2-pyridinecarbonitrile

HRID 2283179Notes

Reaction equation

HRID 2283179 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10](Cl)[C:11]([C:14]#[N:15])=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.C[O-].[Na+].CO.CCCCCC.[C:28](OCC)(=[O:30])C>O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([O:30][CH3:28])[C:11]([C:14]#[N:15])=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 21226206Ethyl acetate hexaneHCID 71075900HCID 71075900, compound2×

Product 1

HCID 710757015-(3-Chlorophenyl)-3-methoxy-2-pyridinecarbonitrileYield 96%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 500 mL round bottom flask adapted for magnetic stirring and fitted with a reflux condenser and nitrogen inlet was charged with 5-(3-chlorophenyl)-3-chloro-2-cyanopyridine, 1, (10 g, 40 mmol), sodium methoxide (13.8 mL, 60 mmol) and methanol (200 mL). With stirring, the reaction solution was heated to reflux for 20 hours. The reaction was determined to be complete due to the disappearance of 5-(3-chlorophenyl)-3-chloro-2-cyanopyridine as measured by TLC analysis using hexane/ethyl acetate (6:3) as the mobile phase and UV 435 nm to visualize the reaction components. The reaction mixture was cooled to room temperature and combined with water (500 mL). A solid began to form. The mixture was cooled to 0° C. to 5° C. and stirred for 3 hours. The resulting solid was collected by filtration and washed with water, then hexane. The resulting cake was dried in vacuo at 40° C. to afford 9.4 g (96% yield) of the desired product as an off-white solid. 1H NMR (DMSO-d6) δ 8.68 (d, 1H), 8.05 (d, 1H), 8.01 (s, 1H) 7.86 (m, 1H), 7.59 (s, 1H), 7.57 (s, 1H) and 4.09 (s, 3H).

Workup

  1. customTo a 500 mL round bottom flask adapted
  2. customfitted with a reflux condenser and nitrogen inlet
  3. stirringWith stirring
  4. temperaturethe reaction solution was heated
  5. temperatureto reflux for 20 hours
  6. customthe reaction components
  7. customto form
  8. temperatureThe mixture was cooled to 0° C. to 5° C.
  9. stirringstirred for 3 hours
  10. filtrationThe resulting solid was collected by filtration
  11. washwashed with water
  12. customThe resulting cake was dried in vacuo at 40° C.

Sources & evidence

ORD record
ord-d76095ba7b634a40bb113eed37960cb8
Source dataset
uspto-grants-2015_09
Patent number
US09145366B2

Reaction notes

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