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 279181

Reaktionsgleichung

Reaktionsgleichung von HRID 279181
[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]

Komponenten

6

Edukt 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

Produkt 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)-imidazoloneAusbeute 38,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-5b91f92a8dc044558d7e78bfa48d68de
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06362206B1

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