Lithium Hydroxide → 5-difluoromethyl-2-methyl-4-(2-methyl-5-phenylbenzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 1883628Notes

Reaction equation

HRID 1883628 reaction equation
[F:1][CH:2]([F:10])[C:3]1[NH:4][C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[OH-].[Li+].[I-].[Na+].[CH3:15][C:16]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:20][C:17]=1[CH2:18]Cl>C1(C)C=CC=CC=1>[F:1][CH:2]([F:10])[C:3]1[N:4]([CH2:18][C:17]2[CH:20]=[C:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:22]=[CH:23][C:16]=2[CH3:15])[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[F:1][CH:2]([F:10])[C:3]1[N:4]=[C:5]([O:9][CH2:18][C:17]2[CH:20]=[C:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:22]=[CH:23][C:16]=2[CH3:15])[N:6]([CH3:8])[N:7]=1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 5238Sodium IodideHCID 235082292-Methyl-5-phenylbenzyl chlorideHCID 1358382515-(Difluoromethyl)-2-methyl-1H-1,2,4-triazol-3(2H)-one

Product 2

HCID 120565215-difluoromethyl-2-methyl-4-(2-methyl-5-phenylbenzyl)-2,4-dihydro-3H-1,2,4-triazol-3-oneHCID 235082143-difluoromethyl-1-methyl-5-(2-methyl-5-phenylbenzyloxy)-1H-1,2,4-triazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixed suspension of 69 mg (0.461 mmol) of 5-difluoromethyl-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (produced in the same manner as in Intermediate Production Example), 12 mg (0.508 mmol) of lithium hydroxide, 14 mg (0.092 mmol) of sodium iodide and 3 ml of toluene was stirred for 2 hours while heating under reflux. Toluene was distilled off under reduced pressure, 3 ml of anhydrous 1,4-dioxane was added to the residue under nitrogen atmosphere, then, 100 mg (0.461 mmol) of 2-methyl-5-phenylbenzyl chloride was added. The reaction solution was stirred for 18 hours while heating under reflux, then, concentrated. Ethyl acetate was added to the residue, the mixture was washed with water, then, washed with saturated saline, and dried over anhydrous magnesium sulfate, then, concentrated. The residue was subjected to silica gel thin layer chromatography (eluant: hexane/ethyl acetate=3/1 (v/v)), to obtain 61 mg of 5-difluoromethyl-2-methyl-4-(2-methyl-5-phenylbenzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 1) and 11 mg of 3-difluoromethyl-1-methyl-5-(2-methyl-5-phenylbenzyloxy)-1H-1,2,4-triazole as a by-product.

Workup

  1. temperaturewhile heating
  2. temperatureunder reflux
  3. distillationToluene was distilled off under reduced pressure, 3 ml of anhydrous 1,4-dioxane
  4. additionwas added to the residue under nitrogen atmosphere
  5. stirringThe reaction solution was stirred for 18 hours
  6. temperaturewhile heating
  7. temperatureunder reflux
  8. concentrationconcentrated
  9. additionEthyl acetate was added to the residue
  10. washthe mixture was washed with water
  11. washwashed with saturated saline
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-7914c2f9fc804d65bfc0b314e8603f6c
Source dataset
uspto-grants-2004_07
Patent number
US06762197B2

Reaction notes

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