Methyl iodide → 1-(4-chloro-2-fluoro-5-methoxyphenyl)-3-difluoromethyl-4,5-dihydro-4-methyl-1,2,4-triazol-5(1H)-one

HRID 2073684Notes

Reaction equation

HRID 2073684 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([N:10]2[C:14](=[O:15])[NH:13][C:12]([CH:16]([F:18])[F:17])=[N:11]2)=[C:4]([F:19])[CH:3]=1.[C:20](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([N:10]2[C:14](=[O:15])[N:13]([CH3:20])[C:12]([CH:16]([F:17])[F:18])=[N:11]2)=[C:4]([F:19])[CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 1360002821-(4-chloro-2-fluoro-5-methoxyphenyl)-3-difluoromethyl-4,5-dihydro-1,2,4-triazol-5(1H)-one

Product 1

HCID 148536521-(4-chloro-2-fluoro-5-methoxyphenyl)-3-difluoromethyl-4,5-dihydro-4-methyl-1,2,4-triazol-5(1H)-oneYield 77.6%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A stirred mixture of 2.0 g (0.0067 mole) of 1-(4-chloro-2-fluoro-5-methoxyphenyl)-3-difluoromethyl-4,5-dihydro-1,2,4-triazol-5(1H)-one and 2.1 g (0.015 mole) of potassium carbonate in 50 mL of acetone was heated at reflux for 30 minutes forming a thick slurry. Iodomethane (4.3 g, 0.03 mole) was added in one portion to the refluxing reaction mixture. After complete addition the mixture was stirred at reflux for 45 minutes. The mixture was cooled to room temperature and the solvent evaporated under reduced pressure leaving a solid residue. This residue was partitioned between water and methylene chloride. The two phase mixture was filtered through a celite pad. The organic phase was removed and was washed in succession with four portions of an aqueous 10% sodium hydroxide solution, and one portion each of an aqueous 10% hydrochloric acid solution, a saturated aqueous sodium carbonate solution, and water. After washing, the organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 1.6 g of 1-(4-chloro-2-fluoro-5-methoxyphenyl)-3-difluoromethyl-4,5-dihydro-4-methyl-1,2,4-triazol-5(1H)-one. A portion of this material was recrystallized from ethanol and water to provide the product as a light tan solid (mp 127°-129° C.), Compound 22.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 30 minutes
  3. customforming a thick slurry
  4. additionAfter complete addition the mixture
  5. temperatureat reflux for 45 minutes
  6. customthe solvent evaporated under reduced pressure
  7. customleaving a solid residue
  8. customThis residue was partitioned between water and methylene chloride
  9. filtrationThe two phase mixture was filtered through a celite pad
  10. customThe organic phase was removed
  11. washwas washed in succession with four portions of an aqueous 10% sodium hydroxide solution, and one portion each of an aqueous 10% hydrochloric acid solution
  12. washAfter washing
  13. dry with materialthe organic phase was dried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-94d43a33fdee4be9bdc3138f53f4bdbd
Source dataset
uspto-grants-1990_04
Patent number
US04919708

Reaction notes

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