Reaktion #1109848

Reaktionsgleichung

Water

Sodium hydrogen carbonate

hydroxylamine monohydrochloride

tert-butyl (6RS,7SR)-6-(3-cyano-2-oxopyridin-1(2H)-yl)-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate

→

title compound

Ausbeute 49.7%

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

Ausbeute 49.7%

Lösungsmittel

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 magnesium sulfate
4. 4
   SonstigeThe solvent was evaporated under reduced pressure
5. 5
   workup.DISSOLUTIONThe residue was dissolved in THF (10 mL)
6. 6
   workup.ADDITIONdiazabicycloundecene (0.032 mL) and CDI (52 mg) were added
7. 7
   Temperaturthe mixture was heated
8. 8
   Temperaturunder reflux for 1 hr
9. 9
   workup.ADDITIONTo the reaction mixture was added 1 N aqueous hydrochloric acid solution
10. 10
    Extraktionthe mixture was extracted with ethyl acetate
11. 11
    WaschenThe extract was washed with water and brine
12. 12
    Trocknendried over anhydrous magnesium sulfate
13. 13
    SonstigeThe solvent was evaporated under reduced pressure
14. 14
    SonstigeThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Vorschrift

Sodium hydrogen carbonate (145 mg) and hydroxylamine monohydrochloride (120 mg) were added to a solution of tert-butyl (6RS,7SR)-6-(3-cyano-2-oxopyridin-1(2H)-yl)-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate (100 mg) in DMSO (4 mL), and the mixture was stirred at 80° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in THF (10 mL), diazabicycloundecene (0.032 mL) and CDI (52 mg) were added, and the mixture was heated under reflux for 1 hr. To the reaction mixture was added 1 N aqueous hydrochloric acid solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (56 mg).

Quelle