Water → HCID 57003299, compound

HRID 1077895Notes

Reaction equation

HRID 1077895 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[N:6][CH:5]=[N:4]1.[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]1([O:36][CH2:35]1)[C@H:17]([N:19]1[CH:23]=[CH:22][N:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)[C:20]1=[O:34])[CH3:18].O>CN(C)C=O.C(OCC)(=O)C>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]([OH:36])([CH2:35][N:3]1[CH:7]=[N:6][CH:5]=[N:4]1)[C@H:17]([N:19]1[CH:23]=[CH:22][N:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:31])([F:33])[F:32])=[CH:26][CH:25]=2)[C:20]1=[O:34])[CH3:18]

Participants

7

Reactant 4

HCID 962WaterHCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 15285741HCID 15285741, compound

Product 1

HCID 57003299HCID 57003299, compoundYield 82.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

60% Sodium hydride in oil (65 mg) was dispersed in 4 ml of dimethylformamide, and 118 mg of 1,2,4-triazole was added thereto with ice cooling. The resulting mixture was stirred at room temperature for ten minutes. The solution of 362 mg of 1-[(1R,2S)-2-(2,4-difluorophenyl)-2,3-epoxy-1-methylpropyl]-3-(4-trifluoromethylphenyl)-2(1H,3H)-imidazolone prepared hereinabove in 2 ml of dimethylformamide was added thereto and the resulting mixture was heated at 50° C. for five hours. After cooling, to the reaction solution was added 8 ml of cold water and 40 ml of ethyl acetate to fractionate and the aqueous layer was extracted with ethyl acetate twice. The ethyl acetate layers were combined, washed with water and a saturated aqueous solution of sodium chloride successively, dried over anhydrous magnesium sulfate and distilled off under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate/hexane=1/1 to 2/1 to ethyl acetate) to give 350 mg of 1-[(1R,2S)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-(4-trifluoromethylphenyl)-2(1H,3H) -imidazolone as a colorless powder.

Workup

  1. additionwas added
  2. temperaturethe resulting mixture was heated at 50° C. for five hours
  3. temperatureAfter cooling, to the reaction solution
  4. extractionthe aqueous layer was extracted with ethyl acetate twice
  5. washwashed with water
  6. dry with materiala saturated aqueous solution of sodium chloride successively, dried over anhydrous magnesium sulfate
  7. distillationdistilled off under reduced pressure
  8. customThe residue was purified by silica gel chromatography (eluent: ethyl acetate/hexane=1/1 to 2/1 to ethyl acetate)

Sources & evidence

ORD record
ord-d91b1c141ba144b4b6b86ccf7ff5f1e4
Source dataset
uspto-grants-1996_08
Patent number
US05545652

Reaction notes

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