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

HRID 1636698Notes

Reaction equation

HRID 1636698 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH:16]=[CH:15][NH:14][C:13]3=[O:17])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[N:2]1.CN1CCCC1=O.[H-].[Na+].[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[C@@:35]1([CH2:39][N:40]2[CH:44]=[N:43][CH:42]=[N:41]2)[C@H:37]([CH3:38])[O:36]1>C(OCC)(=O)C>[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[C@@:35]([OH:36])([CH2:39][N:40]1[CH:44]=[N:43][CH:42]=[N:41]1)[C@H:37]([N:14]1[CH:15]=[CH:16][N:12]([C:9]2[CH:10]=[CH:11][C:6]([N:1]3[CH:5]=[CH:4][N:3]=[N:2]3)=[CH:7][CH:8]=2)[C:13]1=[O:17])[CH3:38]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 24758Sodium hydrideHCID 101311911-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-HCID 108231651-[4-(1H-1,2,3-triazol-1-yl)phenyl]-2(1H,3H)-imidazolone

Product 1

HCID 30029651-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1,2,3-triazol-1-yl)phenyl]-2(1H,3H)-imidazoloneYield 38.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 1-[4-(1H-1,2,3-triazol-1-yl)phenyl]-2(1H,3H)-imidazolone (2.72 g) and 1-methyl-2-pyrrolidone (100 ml) was added sodium hydride (70% in oil, 0.40 g), and the mixture was stirred at room temperature for 1 hour. (2R,3S)-2-(2,4-Difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane (2.51 g) was added thereto, and the mixture was stirred at 100° C. for 8 hours under an argon atmosphere. After cooling, the reaction solution was diluted with ethyl acetate (400 ml), and washed with water (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 concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent:ethyl acetate to ethyl acetate/acetone=5/1) and recrystallized from ethyl acetate-diisopropyl ether 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-1,2,3-triazol-1-yl)phenyl]-2(1H,3H) -imidazolone (Compound 11; 1.82 g) as a pale yellow crystalline powder.

Workup

  1. stirringthe mixture was stirred at 100° C. for 8 hours under an argon atmosphere
  2. temperatureAfter cooling
  3. washwashed with water (100 ml), 1N-hydrochloric acid (100 ml×2)
  4. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (eluent:ethyl acetate to ethyl acetate/acetone=5/1)
  7. customrecrystallized from ethyl acetate-diisopropyl ether

Sources & evidence

ORD record
ord-296aaa5334ac46b28626e6cd1d80fd04
Source dataset
uspto-grants-2000_03
Patent number
US06034248

Reaction notes

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