Reaktion #557848

Reaktionsgleichung

Cerium (IV) diammonium nitrate

sodium hydroxide

compound

(3′S,4′R,7′S,8′S,8a′R)-6″-chloro-8′-(3-chloro-2-fluorophenyl)-4,4-dimethyl-3′,4′-diphenyl-3′,4′,8′,8a′-tetrahydro-1′H-dispiro[cyclohexane-1,6′-pyrrolo[2,1-c][1,4]oxazine-7′,3″-indole]-1′,2″(1″H)-dione

potassium carbonate

hydrochloric acid

→

title compound

Ausbeute 57.0%

(4′S,5′R)-6″-chloro-4′-(3-chloro-2-fluorophenyl)-4,4-dimethyl-2″-oxo-1″,2″-dihydrodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indole]-5′-carboxylic acid

Ausbeute 57.0%

Lösungsmittel

methanol

water

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe resulting mixture was heated
2. 2
   Temperaturto reflux overnight
3. 3
   TemperaturAfter cooling
4. 4
   workup.STIRRINGthe resulting mixture was further stirred for 30 minutes
5. 5
   SonstigeInsoluble matter was removed by filtration through celite
6. 6
   Einengenthe filtrate was concentrated under reduced pressure
7. 7
   workup.ADDITIONThe residue was diluted with water
8. 8
   Extraktionfollowed by extraction with ethyl acetate
9. 9
   ExtraktionThe aqueous layer was further subjected to extraction with chloroform
10. 10
    Trocknendried over anhydrous sodium sulfate
11. 11
    Sonstigethe solvent was evaporated under reduced pressure
12. 12
    Sonstigethe residue was dried

Vorschrift

1N sodium hydroxide solution (50 ml, 50 mmol) was added to a methanol (250 ml) solution of the compound (15.7 g, 23.4 mmol) obtained in Step 1 of Example 1 and the resulting mixture was heated to reflux overnight. After cooling, methanol (500 ml) and water (200 ml) were added to the reaction mixture and then the resulting mixture was neutralized by addition of 1N hydrochloric acid (50 ml) under ice cooling. Cerium (IV) diammonium nitrate (26.9 g, 49.1 mmol) was added under ice cooling, the resulting mixture was stirred for 20 minutes, then potassium carbonate (13.6 g, 98.3 mmol) was added and the resulting mixture was further stirred for 30 minutes. Insoluble matter was removed by filtration through celite and the filtrate was concentrated under reduced pressure. The residue was diluted with water, followed by extraction with ethyl acetate. The aqueous layer was further subjected to extraction with chloroform:methanol [5:1 (v/v)], the organic layers were combined and dried over anhydrous sodium sulfate, then the solvent was evaporated under reduced pressure and the residue was dried to give 6.54 g (57%) of the title compound as a pale yellow solid.

Quelle