Chlorodifluoromethane → 2-(4-Chloro-2-fluoro-5-methoxyphenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 1382135Notes

Reaction equation

HRID 1382135 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]([CH3:16])=[N:11]2)=[C:4]([F:17])[CH:3]=1.[OH-].[Na+].Cl[CH:21]([F:23])[F:22]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1CCCCC1>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([N:10]2[C:14](=[O:15])[N:13]([CH:21]([F:23])[F:22])[C:12]([CH3:16])=[N:11]2)=[C:4]([F:17])[CH:3]=1

Participants

6

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 14798Sodium HydroxideHCID 135688047HCID 135688047, compound

Product 1

HCID 139618062-(4-Chloro-2-fluoro-5-methoxyphenyl)-4-(difluoromethyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 41.7%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 8078CyclohexaneSolvent

Conditions

Temperature
60 °C

Procedure

A stirred mixture of 10.0 g (0.039 mole) of 1-(4-chloro-2-fluoro-5-methoxyphenyl)-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one, 10.0 g (0.031 mole) of tetrabutylammonium bromide and 10.0 grams (0.25 mole) of sodium hydroxide in 250 mL of cyclohexane was warmed to 60° C. Chlorodifluoromethane (10.0 g, 0.12 mole) was bubbled into the reaction mixture. After complete addition the reaction mixture was warmed to reflux where it stirred for one hour. The hot solution was decanted from a pot residue and cooled to ambient temperature. Methylene chloride was added to the cooled mixture to dissolve a solid precipitate. The mixture was washed with 10% hydrochloric acid then with an aqueous 10% sodium hydroxide solution. The organic layer was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield 5.0 g of 1-(4-chloro-2-fluoro-5-methoxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one; mp 86°-88° C.

Workup

  1. additionAfter complete addition the reaction mixture
  2. temperaturewas warmed
  3. temperatureto reflux where it
  4. customThe hot solution was decanted from a pot residue
  5. temperaturecooled to ambient temperature
  6. additionMethylene chloride was added to the cooled mixture
  7. dissolutionto dissolve a solid precipitate
  8. washThe mixture was washed with 10% hydrochloric acid
  9. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-777cdcbf71574f21b2f06da370b6e2c3
Source dataset
uspto-grants-1989_02
Patent number
US04806145

Reaction notes

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