Sodium Iodide → 3-ethyl-6-methyl-5-(1,2,4-oxadiazol-5-yl)-1H-pyridin-2-one

HRID 1921362Notes

Reaction equation

HRID 1921362 reaction equation
[CH2:1]([C:3]1[C:4]([O:15]C)=[N:5][C:6]([CH3:14])=[C:7]([C:9]2[O:13][N:12]=[CH:11][N:10]=2)[CH:8]=1)[CH3:2].[I-].[Na+].Cl[Si](C)(C)C>C(#N)C>[CH2:1]([C:3]1[C:4](=[O:15])[NH:5][C:6]([CH3:14])=[C:7]([C:9]2[O:13][N:12]=[CH:11][N:10]=2)[CH:8]=1)[CH3:2]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 674923793-Ethyl-2-methoxy-6-methyl-5-(1,2,4-oxadiazol-5-yl)pyridine

Product 1

HCID 1354251213-ethyl-6-methyl-5-(1,2,4-oxadiazol-5-yl)-1H-pyridin-2-oneYield 71.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-ethyl-2-methoxy-6-methyl-5-(1,2,4-oxadiazol-5-yl)pyridine (36 mg, 0.164 mmol) and sodium iodide (74 mg, 0.493 mmol) under a nitrogen atmosphere is added anhydrous acetonitrile (3 mL) followed by chlorotrimethylsilane (62 μL, 0.494 mmol) drop-wise. The reaction mixture is stirred at 60° C. under nitrogen for 12 hr. The reaction mixture is allowed to cool and then quenched with water (0.5 mL). After stirring for 30 min the mixture is diluted with water and extracted with five portions of dichloromethane. The combined dichloromethane layer is dried over magnesium sulfate and evaporated. The crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1, increasing to 19:1). Fractions containing the product are combined, the solvent evaporated and the residue triturated with heptane to give 3-ethyl-6-methyl-5-(1,2,4-oxadiazol-5-yl)-1H-pyridin-2-one (24 mg, 71% yield) as a white solid. LC/MS: RT: 2.37 min, MS: m/e=206 (M+H); 1H NMR (CDCl3, δ, ppm): 12.56 (1H, s), 8.44 (1H, s), 7.96 (1H, s), 2.82 (3H, s), 2.62 (2H, q), 1.26 (3H, t).

Workup

  1. temperatureto cool
  2. customquenched with water (0.5 mL)
  3. stirringAfter stirring for 30 min the mixture
  4. additionis diluted with water
  5. extractionextracted with five portions of dichloromethane
  6. dry with materialThe combined dichloromethane layer is dried over magnesium sulfate
  7. customevaporated
  8. customThe crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1, increasing to 19:1)
  9. additionFractions containing the product
  10. customthe solvent evaporated
  11. customthe residue triturated with heptane

Sources & evidence

ORD record
ord-e4d428139ee84f54bcbcb5dfbfa086d8
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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