1H-1,2,4-Triazole → HCID 86751398, compound

HRID 1489434Notes

Reaction equation

HRID 1489434 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[CH:16]=[CH:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:30])([F:29])[CH:26]([F:28])[F:27])=[CH:19][CH:18]=2)[C:13]1=[O:31])[CH3:11].[NH:39]1[CH:43]=[N:42][CH:41]=[N:40]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[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[CH:16]=[CH:15][N:14]([C:17]2[CH:18]=[CH:19][C:20]([O:23][CH2:24][C:25]([F:29])([F:30])[CH:26]([F:27])[F:28])=[CH:21][CH:22]=2)[C:13]1=[O:31])[CH3:11]

Participants

6

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 10674539HCID 10674539, compound

Product 1

HCID 86751398HCID 86751398, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

1-[(1R, 2S)-2-(2,4-Difluorophenyl)-2-hydroxy-3-methanesulfonyloxy-1-methylpropyl]-3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2(1H, 3H)-imidazolone(0.55 g) was dissolved in 15 ml of dimethylformamide, to which 0.329 g of 1H-1,2,4-triazole and 1.34 g of potassium carbonate were added. The mixture was heated at 90° C. for 5 hours. After cooling, the reaction solution was diluted with 60 ml of ethyl acetate, and washed with 30 ml of water, 1N-hydrochloric acid (30 ml×2) and 30 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: 50 g, eluent; hexane:ethyl acetate=2:1). The desired fraction was concentrated and the residue was recrystallized from a mixture of 2 ml of ethyl acetate and 10 ml of diisopropyl ether to give 0.25 g of 1-[(1R,2S)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2(1H,3H)-imidazolone (yield: 47%) as colorless powdery crystals.

Workup

  1. additionwere added
  2. temperatureAfter cooling
  3. washwashed with 30 ml of water, 1N-hydrochloric acid (30 ml×2) and 30 ml of an aqueous solution of sodium chloride successively
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. distillationAfter the solvent was distilled off under reduced pressure
  6. customthe residue was purified by silica gel chromatography (silica gel: 50 g, eluent; hexane:ethyl acetate=2:1)
  7. concentrationThe desired fraction was concentrated
  8. customthe residue was recrystallized from a mixture of 2 ml of ethyl acetate and 10 ml of diisopropyl ether

Sources & evidence

ORD record
ord-1240f5f8698d487598bbd8eaa1deadb7
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

Loading…