Potassium Carbonate → HCID 11708269, compound

HRID 1921347Notes

Reaction equation

HRID 1921347 reaction equation
Br[C:2]1[C:3]([CH3:12])=[N:4][C:5]([O:10]C)=[C:6]([CH2:8][CH3:9])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[NH:19]1[CH:23]=[CH:22][N:21]=[N:20]1>[Cu](I)I>[CH2:8]([C:6]1[C:5](=[O:10])[NH:4][C:3]([CH3:12])=[C:2]([N:20]2[N:21]=[CH:22][CH:23]=[N:19]2)[CH:7]=1)[CH3:9]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 116586693-Bromo-5-ethyl-6-methoxy-2-methylpyridineHCID 178418936HCID 178418936, compound

Product 1

HCID 11708269HCID 11708269, compoundYield 11.3%

Reagents, catalysts & solvents 1

HCID 83717Copper iodideCatalyst

Conditions

Temperature
185 °C

Procedure

Into a microwave vial is added 3-bromo-5-ethyl-6-methoxy-2-methyl-pyridine (400 mg, 1.74 mmol), potassium carbonate (360 mg, 2.61 mmol), copper iodide (50 mg, 0.263 mmol) and 1,2,3-triazole (201 μL, 3.47 mmol). The vial is flushed with nitrogen before anhydrous dimethylformamide (4 mL) is added then sealed. The reaction is heated in the CEM Discover microwave at 185° C. for 20 min (4 bar pressure attained). LC/MS shows the reaction is incomplete. The reaction is re-microwaved to 180° C. for 20 min. Further copper iodide (50 mg) is added, the reaction flushed with nitrogen and is re-microwaved to 180° C. for 20 min. LC/MS shows the reaction is complete with the formation of 2 materials. The reaction is diluted with water and extracted with six portions of dichloromethane. The combined extracts are then dried over magnesium sulfate and evaporated to give a dark oil. The crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (3:1, increasing to 2:1 then 1:1). Fractions containing the higher Rf product are combined, the solvent evaporated and the residue is triturated twice with heptane and twice with ether to give 3-ethyl-6-methyl-5-(1,2,3-triazol-2-yl)-1H-pyridin-2-one (40 mg, 11% yield) as a white powder. LC/MS: RT: 2.19 min, MS: m/e=205 (M+H); 1H NMR (δ, ppm): 11.93 (1H, s), 8.04 (2H, s), 7.40 (1H, s), 2.41 (2H, q), 2.06 (3H, s), 1.09 (3H, t).

Workup

  1. customThe vial is flushed with nitrogen before anhydrous dimethylformamide (4 mL)
  2. additionis added
  3. customthen sealed
  4. customThe reaction is re-microwaved to 180° C. for 20 min
  5. additionFurther copper iodide (50 mg) is added
  6. customthe reaction flushed with nitrogen
  7. customis re-microwaved to 180° C. for 20 min
  8. additionThe reaction is diluted with water
  9. extractionextracted with six portions of dichloromethane
  10. dry with materialThe combined extracts are then dried over magnesium sulfate
  11. customevaporated
  12. customto give a dark oil
  13. customThe crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (3:1
  14. temperatureincreasing to 2:1
  15. additionFractions containing the higher Rf product
  16. customthe solvent evaporated
  17. customthe residue is triturated twice with heptane and twice with ether

Sources & evidence

ORD record
ord-7ff7cfa356ab49b59aff45ec0bc3f85d
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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