Methyl iodide → 2-Methoxy-5-(3-methylsulfanyl-[1,2,4]triazol-4-yl)-benzoic acid methyl ester

HRID 2230743Notes

Reaction equation

HRID 2230743 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[C:8]([N:10]2[C:14](=[S:15])[NH:13][N:12]=[CH:11]2)[CH:7]=[CH:6][C:5]=1[O:16][CH3:17].[C:19](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[C:8]([N:10]2[CH:11]=[N:12][N:13]=[C:14]2[S:15][CH3:19])[CH:7]=[CH:6][C:5]=1[O:16][CH3:17]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 865839052-Methoxy-5-(5-thioxo-1,5-dihydro-[1,2,4]triazol-4-yl)-benzoic acid methyl ester

Product 1

HCID 701482672-Methoxy-5-(3-methylsulfanyl-[1,2,4]triazol-4-yl)-benzoic acid methyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Treat a stirred mixture of 2-methoxy-5-(5-thioxo-1,5-dihydro-[1,2,4]triazol-4-yl)-benzoic acid methyl ester (3.80 g, 14.38 mmol), potassium carbonate (2.19 g, 15.8 mmol) and anhydrous acetone (60 mL) with methyl iodide (1.07 mL, 17.25 mmol) added dropwise via syringe. Reflux the stirred mixture for 2.5 hours, cool, filter and wash the filter cake twice with acetone. Combine the acetone phases, concentrate in vacuo, dissolve the residue in ethyl acetate and wash with NaHCO3 solution. Extract the combined aqueous phases three times with ethyl acetate. Combine the ethyl acetate phases, wash with saturated NaHCO3 and brine, dry (MgSO4), filter and concentrate in vacuo to afford an oil. Purify the oil by flash chromatography (silica gel, 5.5×15.2 cm) eluting with ethyl acetate and then with 5% methanol in dichloromethane after elution of the starting material. Concentrate the appropriate fractions to afford 2.89 g of 2-methoxy-5-(3-methylsulfanyl-[1,2,4]triazol-4-yl)-benzoic acid methyl ester as a colorless solid.

Workup

  1. additionTreat
  2. additionadded dropwise via syringe
  3. temperatureReflux the stirred mixture for 2.5 hours
  4. temperaturecool
  5. filtrationfilter
  6. washwash the filter cake twice with acetone
  7. concentrationconcentrate in vacuo
  8. dissolutiondissolve the residue in ethyl acetate
  9. washwash with NaHCO3 solution
  10. extractionExtract the combined aqueous phases three times with ethyl acetate
  11. washwash with saturated NaHCO3 and brine
  12. dry with materialdry (MgSO4)
  13. filtrationfilter
  14. concentrationconcentrate in vacuo
  15. customto afford an oil
  16. customPurify the oil by flash chromatography (silica gel, 5.5×15.2 cm)
  17. washeluting with ethyl acetate
  18. washwith 5% methanol in dichloromethane after elution of the starting material
  19. concentrationConcentrate the appropriate fractions

Sources & evidence

ORD record
ord-9c7e30a35b5244b09a1df6bb0f424f01
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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