Acetic Acid → 3-(5-Ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrile

HRID 1921364Notes

Reaction equation

HRID 1921364 reaction equation
CN(C)C(=N[C:6](=O)[C:7]1[CH:12]=[C:11]([CH2:13][CH3:14])[C:10]([O:15]C)=[N:9][C:8]=1[CH3:17])C.Cl.NO.[OH-].[Na+].[C:25](O)(=O)[CH3:26]>O1CCOCC1.O>[CH2:13]([C:11]1[C:10](=[O:15])[NH:9][C:8]([CH3:17])=[C:7]([C:6]2[CH:6]=[C:7]([CH:12]=[CH:25][CH:26]=2)[C:8]#[N:9])[CH:12]=1)[CH3:14]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 67492454N-(1-dimethylaminoethylidene)-5-ethyl-6-methoxy-2-methylnicotinamide

Product 1

HCID 116300653-(5-Ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrileYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

In a round bottom flask under a nitrogen atmosphere a mixture of N-(1-dimethylaminoethylidene)-5-ethyl-6-methoxy-2-methylnicotinamide (synthesized on 1.00 mmol scale), hydroxylamine hydrochloride (83.4 mg, 1.2 mmol), sodium hydroxide (48 mg, 1.2 mmol) and glacial acetic acid (1.4 mL) is treated with water (0.7 mL) and 1,4-dioxane (1 mL). The resulting dark mixture is stirred at 90° C. for 35 min. The reaction mixture is partitioned between water and ethyl acetate. The mixture is treated with excess solid sodium bicarbonate, the ethyl acetate layer is separated and the aqueous layer is extracted with 4 further portions of ethyl acetate. The combined ethyl acetate layer is dried over magnesium sulfate and evaporated to give a black residue that is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined, evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (49:1). Fractions containing the product are combined and the solvent evaporated to give 3-ethyl-2-methoxy-6-methyl-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyridine (189 mg, 81% yield, from Steps 1 and 2 above) as a white solid. MS: m/e=234 (M+H); 1H NMR (CDCl3, δ, ppm): 8.01 (1H, s), 4.01 (3H, s), 2.81 (3H, s), 2.60 (2H, q), 2.46 (3H, s), 1.23 (3H, t).

Workup

  1. customThe reaction mixture is partitioned between water and ethyl acetate
  2. additionThe mixture is treated with excess solid sodium bicarbonate
  3. customthe ethyl acetate layer is separated
  4. extractionthe aqueous layer is extracted with 4 further portions of ethyl acetate
  5. dry with materialThe combined ethyl acetate layer is dried over magnesium sulfate
  6. customevaporated
  7. customto give a black residue that
  8. customis purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane
  9. additionFractions containing the product
  10. customevaporated
  11. customre-purified by flash chromatography on a 5-gram silica gel cartridge by elution with heptane:dichloromethane (49:1)
  12. additionFractions containing the product
  13. customthe solvent evaporated

Sources & evidence

ORD record
ord-966dbdecc6804b36baaffb19f4e33ac4
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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