Reaktion #1109817

Reaktionsgleichung

Sodium hydrogen carbonate

hydroxylamine monohydrochloride

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

diazabicycloundecene

1,1′-carbonyldiimidazole

→

title compound

Ausbeute 93.1%

tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-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 93.1%

Lösungsmittel

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.DISSOLUTIONThe residue was dissolved in THF (15 mL)
6. 6
   Temperaturthe mixture was heated
7. 7
   Temperaturunder reflux for 2 hr
8. 8
   EinengenThe reaction mixture was concentrated under reduced pressure, 1 N hydrochloric acid
9. 9
   workup.ADDITIONwas added to the residue
10. 10
    Extraktionthe mixture was extracted with ethyl acetate
11. 11
    WaschenThe extract was washed with brine
12. 12
    Trocknendried over anhydrous sodium sulfate
13. 13
    SonstigeThe solvent was evaporated under reduced pressure
14. 14
    SonstigeThe residue was purified by silica gel column chromatography

Vorschrift

Sodium hydrogen carbonate (2.53 g, 30.14 mmol) and hydroxylamine monohydrochloride (2.094 g, 30.14 mmol) were added to a solution of tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-1,4-oxazepane-4-carboxylate (1.74 g, 3.77 mmol) in DMSO (4 mL), and the mixture was stirred at 80° C. overnight. To the reaction mixture was added 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 dissolved in THF (15 mL), diazabicycloundecene (0.564 mL, 3.77 mmol) and 1,1′-carbonyldiimidazole (0.917 g, 5.66 mmol) were added, and the mixture was heated under reflux for 2 hr. The reaction mixture was concentrated under reduced pressure, 1 N hydrochloric acid was added to the residue, 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 to give the title compound (1.826 g, 3.51 mmol, 93%).

Quelle