1H-1,2,4-Triazole → 2-[3-(2,4-Difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 1489429Notes

Reaction equation

HRID 1489429 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([CH2:32]OS(C)(=O)=O)[C@H:10]([N:12]1[C:16](=[O:17])[N:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])=[CH:20][CH:19]=2)[CH:14]=[N:13]1)[CH3:11].[NH:39]1[CH:43]=[N:42][CH:41]=[N:40]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([CH2:32][N:39]1[CH:43]=[N:42][CH:41]=[N:40]1)[C@H:10]([N:12]1[C:16](=[O:17])[N:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([F:31])([F:30])[CH:27]([F:28])[F:29])=[CH:20][CH:19]=2)[CH:14]=[N:13]1)[CH3:11]

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 10578947HCID 10578947, compound

Product 1

HCID 4796552-[3-(2,4-Difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

2-[(1R,2S)-2-(2,4-Difluorophenyl)-2-hydroxy-3-methanesulfonyloxy-1-methylpropyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (10 g) was dissolved in 180 ml of dimethylformamide, to which 5.7 g of 1H-1,2,4-triazole and 23.2 g of potassium carbonate were added. The mixture was heated at 90° C. for 5 hours. The reaction solution was concentrated under reduced pressure to ca. 100 ml and diluted with a mixture of 400 ml of ethyl acetate and 200 ml of diisopropyl ether. The mixture was washed with 100 ml of water, 1N-hydrochloric acid (100 ml×2) and 100 ml of an aqueous solution of sodium chloride successively. The organic layer was dried over magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel chromatography (silica gel: 70 g, eluent; hexane:ethyl acetate=3:4 to ethyl acetate). The desired fraction was concentrated and the residue was recrystallized from a mixture of 10 ml of ethyl acetate and 80 ml of diisopropyl ether to give 7.3 g of 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (yield: 80%) as a colorless powdery crystals.

Workup

  1. additionwere added
  2. concentrationThe reaction solution was concentrated under reduced pressure to ca. 100 ml
  3. additiondiluted with a mixture of 400 ml of ethyl acetate and 200 ml of diisopropyl ether
  4. washThe mixture was washed with 100 ml of water, 1N-hydrochloric acid (100 ml×2) and 100 ml of an aqueous solution of sodium chloride successively
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. distillationAfter the solvent was distilled off under reduced pressure
  7. customthe residue was purified by silica gel chromatography (silica gel: 70 g, eluent; hexane:ethyl acetate=3:4 to ethyl acetate)
  8. concentrationThe desired fraction was concentrated
  9. customthe residue was recrystallized from a mixture of 10 ml of ethyl acetate and 80 ml of diisopropyl ether

Sources & evidence

ORD record
ord-c89718968e1347a78030b667d031a581
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

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