Hydrogen Peroxide → 3-Desoxy-3-carboxamidonaltrexone

HRID 2384595Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2384595
[CH:1]1([CH2:4][N:5]2[CH2:24][CH2:23][C@:12]34[C:13]5[C:14]6[O:22][C@H:11]3[C:10](=[O:25])[CH2:9][CH2:8][C@@:7]4([OH:26])[C@H:6]2[CH2:19][C:18]=5[CH:17]=[CH:16][C:15]=6[C:20]#[N:21])[CH2:3][CH2:2]1.C(=O)([O-])[O-:28].[K+].[K+].OO>CS(C)=O.C(Cl)Cl>[CH:1]1([CH2:4][N:5]2[CH2:24][CH2:23][C@:12]34[C:13]5[C:14]6[O:22][C@H:11]3[C:10](=[O:25])[CH2:9][CH2:8][C@@:7]4([OH:26])[C@H:6]2[CH2:19][C:18]=5[CH:17]=[CH:16][C:15]=6[C:20]([NH2:21])=[O:28])[CH2:3][CH2:2]1

Komponenten

6

Edukt 3

HCID 784Hydrogen PeroxideHCID 11430Potassium CarbonateHCID 15425895HCID 15425895, Verbindung

Produkt 1

HCID 100219463-Desoxy-3-carboxamidonaltrexoneAusbeute 71,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To an ice/water cooled suspension of (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carbonitrile [P2] (6.0 g, 17.1 mmol) and potassium carbonate (7.09 g, 51.37 mmol) in DMSO (120 mL) was added hydrogen peroxide (25 mL, 35 wt. % in H2O) drop wise at a rate to ensure the temperature remained below 20° C. The mixture was stirred for 2 hours then diluted with DCM (800 mL). The solution was washed with water (3×500 mL) before the organic phase was dried (MgSO4). Filtration and removal of the solvent under reduced pressure gave crude product that was purified by trituration with methanol giving (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carboxamide [P3] (4.50 g, 71% yield); LC/MS (r.t. 10.1 minutes [5 to 95% B]), 369 (M+H)+.

Aufarbeitung

  1. customremained below 20° C
  2. washThe solution was washed with water (3×500 mL) before the organic phase
  3. dry with materialwas dried (MgSO4)
  4. filtrationFiltration and removal of the solvent under reduced pressure
  5. customgave crude product that
  6. customwas purified by trituration with methanol

Quellen und Nachweise

ORD-Eintrag
ord-675e2dfb2bdc4f28a8596c5cdb60cca5
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08263807B2

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