Reaktion #1109787

Reaktionsgleichung

diazabicycloundecene

Sodium hydrogen carbonate

hydroxylamine hydrochloride

tert-butyl (6R,7R)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate

→

title compound

Ausbeute 72.6%

tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-{[2-oxo-3-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)pyridin-1(2H)-yl]methyl}-1,4-oxazepane-4-carboxylate

Ausbeute 72.6%

Lösungsmittel

THF

water

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionthe mixture was extracted with ethyl acetate
2. 2
   WaschenThe extract was washed with brine
3. 3
   Trocknendried over anhydrous sodium sulfate
4. 4
   SonstigeThe solvent was evaporated under reduced pressure
5. 5
   workup.ADDITIONwere added
6. 6
   workup.STIRRINGthe mixture was stirred at 70° C. for 2 hr
7. 7
   EinengenThe reaction mixture was concentrated under reduced pressure
8. 8
   Extraktionthe mixture was extracted with ethyl acetate
9. 9
   WaschenThe extract was washed with brine
10. 10
    Trocknendried over anhydrous sodium sulfate
11. 11
    SonstigeThe solvent was evaporated under reduced pressure
12. 12
    SonstigeThe residue was purified by silica gel column chromatography
13. 13
    Sonstigerecrystallized from ethanol-hexane

Vorschrift

Sodium hydrogen carbonate (829 mg, 9.87 mmol) and hydroxylamine hydrochloride (686 mg, 9.87 mmol) were added to a solution of tert-butyl (6R,7R)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate (590 mg, 1.23 mmol) in DMSO (4 mL), and the mixture was stirred at 80° C. for 5 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was diluted with THF (10 mL), diazabicycloundecene (0.184 mL, 1.23 mmol) and carbonyl-1,1′-bisimidazole (299 mg, 1.85 mmol) were added, and the mixture was stirred at 70° C. for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was acidified with 1 N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and recrystallized from ethanol-hexane to give the title compound (480 mg, 0.893 mmol, 72.6%).

Quelle