Water → 3-{1-[4-chloro-2-(methylsulfonyl)phenoxy]-1-methylethyl}-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole monohydrochloride

HRID 389143Notes

Reaction equation

HRID 389143 reaction equation
Br[C:2]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:3]=1[O:4][C:5]([C:8]1[N:12]([CH3:13])[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([F:23])([F:22])[F:21])=[N:10][N:9]=1)([CH3:7])[CH3:6].[CH3:29][S:30]([O-:32])=[O:31].[Na+].O.C(OCC)(=O)C>CS(C)=O.[Cu](I)I>[ClH:28].[Cl:28][C:26]1[CH:25]=[CH:24][C:3]([O:4][C:5]([C:8]2[N:12]([CH3:13])[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]([F:23])([F:22])[F:21])=[N:10][N:9]=2)([CH3:7])[CH3:6])=[C:2]([S:30]([CH3:29])(=[O:32])=[O:31])[CH:27]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 2733271Sodium methanesulfinateHCID 582438453-[1-(2-bromo-4-chlorophenoxy)-1-methylethyl]-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole

Product 1

HCID 670244153-{1-[4-chloro-2-(methylsulfonyl)phenoxy]-1-methylethyl}-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole monohydrochlorideYield 16.7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 3-[1-(2-bromo-4-chlorophenoxy)-1-methylethyl]-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole (200 mg), sodium methanesulfinate (215 mg) and copper iodide (400 mg) was dissolved in DMSO, followed by stirring under a nitrogen atmosphere at 110° C. for 4 hours and at 140° C. overnight. The reaction solution was returned to room temperature and water and ethyl acetate were added thereto, followed by celite filtration. The organic layer was separated from the filtrate, washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=97:3) and further purified by thin layer chromatography (chloroform:methanol=97:3). The resulting residue was dissolved in ethyl acetate and 4M hydrogen chloride-ethyl acetate was added thereto, followed by stirring at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure. The resulting residue was crystallized by adding diisopropylether and collected by filtration to obtain 3-{1-[4-chloro-2-(methylsulfonyl)phenoxy]-1-methylethyl}-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole monohydrochloride (18 mg) as a white crystal.

Workup

  1. customwas returned to room temperature
  2. filtrationfollowed by celite filtration
  3. customThe organic layer was separated from the filtrate
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was then evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=97:3)
  8. customfurther purified by thin layer chromatography (chloroform:methanol=97:3)
  9. dissolutionThe resulting residue was dissolved in ethyl acetate
  10. addition4M hydrogen chloride-ethyl acetate was added
  11. stirringby stirring at room temperature for 30 minutes
  12. concentrationThe reaction solution was concentrated under reduced pressure
  13. customThe resulting residue was crystallized
  14. additionby adding diisopropylether
  15. filtrationcollected by filtration

Sources & evidence

ORD record
ord-41e58efaae874a3fb7b35031378da717
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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