Dimethylformamide → 1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1,2,4-triazol-1-yl)phenyl]-2(1H,3H)-imidazolone

HRID 1636697Notes

Reaction equation

HRID 1636697 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]1([CH2:13][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)[C@H:11]([CH3:12])[O:10]1.[N:19]1([C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH:34]=[CH:33][NH:32][C:31]3=[O:35])=[CH:26][CH:25]=2)[CH:23]=[N:22][CH:21]=[N:20]1.C(=O)([O-])[O-].[Cs+].[Cs+].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:10])([CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[C@H:11]([N:32]1[CH:33]=[CH:34][N:30]([C:27]2[CH:26]=[CH:25][C:24]([N:19]3[CH:23]=[N:22][CH:21]=[N:20]3)=[CH:29][CH:28]=2)[C:31]1=[O:35])[CH3:12]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 101311911-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-HCID 106330471-[4-(1H-1,2,4-triazol-1-yl)phenyl]-2-(1H,3H)-imidazolone

Product 1

HCID 30029631-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1,2,4-triazol-1-yl)phenyl]-2(1H,3H)-imidazoloneYield 21.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

(2R,3S)-2-(2,4-Difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane (2.5 g), 1-[4-(1H-1,2,4-triazol-1-yl)phenyl]-2(1H,3H)-imidazolone (2.72 g) and cesium carbonate (powder: 9.7 g) were added to N,N-dimethylformamide (150 ml), and the mixture was heated at 80° C. with stirring for 9.5 hours. After cooling, the reaction mixture was diluted with ethyl acetate (400 ml). Ice water (150 ml) was added thereto to separate the ethyl acetate layer. The aqueous layer was extracted with ethyl acetate (100 ml). The ethyl acetate layers were combined and washed with 0.5N-sodium hydroxide (100 ml), 1N-hydrochloric acid (100 ml×2) and a saturated aqueous solution of sodium chloride (50 ml) successively. The ethyl acetate layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel chromatography (eluent:ethyl acetate/acetone=2/1) to give 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1,2,4-triazol-1-yl)phenyl]-2(1H,3H)-imidazolone (Compound 9; 1.03 g) as a pale yellow powder.

Workup

  1. temperatureAfter cooling
  2. customto separate the ethyl acetate layer
  3. extractionThe aqueous layer was extracted with ethyl acetate (100 ml)
  4. washwashed with 0.5N-sodium hydroxide (100 ml), 1N-hydrochloric acid (100 ml×2)
  5. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent
  8. customThe residue was purified by silica gel chromatography (eluent:ethyl acetate/acetone=2/1)

Sources & evidence

ORD record
ord-903d424f6e6b469c90dbd2ab9dbfb21c
Source dataset
uspto-grants-2000_03
Patent number
US06034248

Reaction notes

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