Sodium hydride → (+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate

HRID 609582Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 609582
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[N:24][NH:23][C:22]4=[O:26])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[H-].[Na+].[CH3:29][C@@H:30](O)[CH2:31]C.Br[C:35]1[CH:40]=C[C:38]([S:41]([O-:44])(=[O:43])=[O:42])=[CH:37][CH:36]=1>CN(C)C=O>[CH3:29][C:30]1([CH3:31])[CH:5]2[CH2:6][CH2:7][C@@:8]1([CH2:38][S:41]([OH:44])(=[O:43])=[O:42])[C:3](=[O:2])[CH2:4]2.[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[N:24][N:23]([C@@H:35]([CH3:40])[CH2:36][CH3:37])[C:22]4=[O:26])=[CH:17][CH:16]=3)[CH2:13][CH2:14]2)=[CH:5][CH:4]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 42465972,4-Dihydro-4-(4-(4-(4-methoxyphenyl)piperazin-1-yl)phenyl)-3H-1,2,4-triazol-3-oneHCID 131721473(R)-2-butanol 4-bromobenzenesulfonate2×

Produkt 1

HCID 131721474(+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonateAusbeute 13,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 3.5 g of (2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-3H-1,2,4-triazol-3-one, 0.6 g of a sodium hydride dispersion 50% and 100 ml of N,N-dimethylformamide was stirred for 3 hours at 80° C. After the addition of 3.5 g of (R)-2-butanol 4-bromobenzenesulfonate (ester) (intermediate (3)), stirring was continued for 6 hours at this temperature. After cooling, waster was added. The crystallized product was filtered off and taken up in trichloromethane. The undissolved part was filtered off. The remaining solution was dried and purified by column chromatography over silica gel using trichloromethane as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 4-methyl-2-pentanone. The product was filtered off and converted into the (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate salt in 2-propanone. The salt was filtered off and recrystallized from 1-butanol. The product was filtered off and dried, yielding 1.2 g (13.7%) of (+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate (1:2); mp. 192.0° C.; [α]D20 =+28.41° (conc.=1% in ethanol) (interm. 5).

Aufarbeitung

  1. stirringstirring
  2. waitwas continued for 6 hours at this temperature
  3. temperatureAfter cooling
  4. additionwaster was added
  5. filtrationThe crystallized product was filtered off
  6. filtrationThe undissolved part was filtered off
  7. customThe remaining solution was dried
  8. custompurified by column chromatography over silica gel
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from 4-methyl-2-pentanone
  12. filtrationThe product was filtered off
  13. filtrationThe salt was filtered off
  14. customrecrystallized from 1-butanol
  15. filtrationThe product was filtered off
  16. customdried

Quellen und Nachweise

ORD-Eintrag
ord-ff3d1fb40ea24d85a6e21c6e0437136d
Quelldatensatz
uspto-grants-1999_12
Patentnummer
US05998413

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