Sodium Methoxide → 5-(3-Chlorophenyl)-3-methoxy-2-pyridinecarbonitrile

HRID 2283183Notes

Reaction equation

HRID 2283183 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+].CCCCCC.[C:26](OCC)(=[O:28])C>O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([O:28][CH3:26])[C:11]([C:14]#[N:15])=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

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

Product 1

HCID 710757015-(3-Chlorophenyl)-3-methoxy-2-pyridinecarbonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

A 20 L reactor equipped with a mechanical stirred, condenser, thermometer and nitrogen inlet was charged with 5-(3-chlorophenyl)-3-chloro-2-cyanopyridine, 1, (558 g, 2.24 mol) and sodium methoxide (25% solution in methanol, 726.0 g, 3.36 mol). With agitation, the reaction solution was heated to reflux for 24 hours, resulting in a beige-colored suspension. 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 5° C. and then charged with water (5580 mL). The resulting slurry was agitated for 3 hours at 5° C. The solid product was isolated by filtration and washed with water (5580 mL) until the filtrate had a pH of 7. The filter cake was air dried under vacuum for 16 hours. The filter cake was then charged back to the reactor and triturated in MeOH (2210 g, 2794 mL) for 1 hour at ambient temperature. The solid was collected by filtration and washed with MeOH (882 g, 1116 mL, 5° C.) followed by heptane (205 mL, 300 mL), and dried under high vacuum at 45° C. for 72 hours to afford 448 g (82% yield) of the desired product as an off-white solid. Purity by HPLC was 97.9%. 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. customA 20 L reactor equipped with a mechanical stirred, condenser, thermometer and nitrogen inlet
  2. temperatureWith agitation, the reaction solution was heated
  3. temperatureto reflux for 24 hours
  4. customresulting in a beige-colored suspension
  5. customthe reaction components
  6. customThe solid product was isolated by filtration
  7. washwashed with water (5580 mL) until the filtrate
  8. customdried under vacuum for 16 hours
  9. additionThe filter cake was then charged back to the reactor
  10. customtriturated in MeOH (2210 g, 2794 mL) for 1 hour at ambient temperature
  11. filtrationThe solid was collected by filtration
  12. washwashed with MeOH (882 g, 1116 mL, 5° C.)
  13. customdried under high vacuum at 45° C. for 72 hours

Sources & evidence

ORD record
ord-cafb86c649784dc78ebf90ce9c6cf635
Source dataset
uspto-grants-2015_09
Patent number
US09145366B2

Reaction notes

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