Reaktion #560148

Reaktionsgleichung

6′-bromo-4,4-difluorospiro[cyclohexane-1,2′-inden]-1′(3′H)-one

3-cyanobenzeneboronic acid

cesium carbonate

→

3-(4,4-difluoro-1′-oxo-1′,3′-dihydrospiro[cyclohexane-1,2′-indene]-6′-yl)benzonitrile

Ausbeute 80.2%

Lösungsmittel

Dioxane water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction vial was capped
2. 2
   FiltrationAt this time, the mixture was filtered through a Celite plug
3. 3
   WaschenThe plug was rinsed with dichloromethane (5 mL) and water (5 mL)
4. 4
   SonstigeThe phases in the filtrate were separated
5. 5
   ExtraktionThe aqueous phase was back-extracted with dichloromethane twice (3 mL/each)
6. 6
   WaschenThe combined organic phases were washed with brine
7. 7
   Trocknendried over MgSO4
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated
10. 10
    SonstigeThe crude material was purified by flash chromatography (ISCO, 12 g SiO2 cartridge, ethyl acetate/hexanes as the eluents)
11. 11
    Einengenconcentrated

Vorschrift

In a 20 mL vial was placed 6′-bromo-4,4-difluorospiro[cyclohexane-1,2′-inden]-1′(3′H)-one (35 mg, 0.111 mmol), 3-cyanobenzeneboronic acid (23 mg, 0.157 mmol), PdCl2(PPh3)2 (8 mg, 0.011 mmol) and cesium carbonate (91 mg, 0.279 mmol). This solid mixture was dissolved in a Dioxane/water mixture (1.1 mL, 6:1 ratio, respectively). The reaction vial was capped and allowed to stir at 90° C. for 1 hour. At this time, the mixture was filtered through a Celite plug. The plug was rinsed with dichloromethane (5 mL) and water (5 mL). The phases in the filtrate were separated. The aqueous phase was back-extracted with dichloromethane twice (3 mL/each). The combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated under reduce pressure. The crude material was purified by flash chromatography (ISCO, 12 g SiO2 cartridge, ethyl acetate/hexanes as the eluents). The corresponding fractions were combined and concentrated under reduce pressure yielding 3-(4,4-difluoro-1′-oxo-1′,3′-dihydrospiro[cyclohexane-1,2′-indene]-6′-yl)benzonitrile (30 mg, 0.089 mmol, 80% yield) as a white solid.

Quelle