Reaktion #1835699

Reaktionsgleichung

2,5-dibromo-3-methylpyridine

sodium bis(trimethylsilyl)amide

1,4-dioxaspiro[4,5]decane-8-carbonitrile

→

1-(5-bromo-3-methylpyridin-2-yl)-4-oxocyclohexanecarbonitrile

Ausbeute 97.6%

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 30 minutes
2. 2
   workup.STIRRINGfurther stirred at room temperature for an hour
3. 3
   Extraktionextracted with ethyl acetate
4. 4
   WaschenThe organic layer was washed with saturated brine
5. 5
   Einengenconcentrated in vacuo
6. 6
   workup.ADDITIONTo the residue, were added trifluoroacetic acid (20 ml) and water (5 ml)
7. 7
   workup.STIRRINGthe mixture was stirred at 40° C. for two hours
8. 8
   workup.ADDITIONThe reaction solution was treated with an aqueous solution of sodium carbonate
9. 9
   Extraktionextracted with ethyl acetate
10. 10
    TrocknenThe organic layer was dried over anhydrous magnesium sulfate
11. 11
    Einengenconcentrated in vacuo
12. 12
    Sonstigethe residue was purified with silica gel column chromatography (ethyl acetate:n-hexane=5:1)

Vorschrift

1M Solution of sodium bis(trimethylsilyl)amide (77 ml) was added under ice cooling to 1,4-dioxaspiro[4,5]decane-8-carbonitrile (11.0 g) described in Reference Example 82(1) and stirred for 30 minutes. Then, 2,5-dibromo-3-methylpyridine (15 g) was added, stirred for 30 minutes and further stirred at room temperature for an hour. The reaction solution was treated with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and concentrated in vacuo. To the residue, were added trifluoroacetic acid (20 ml) and water (5 ml), and the mixture was stirred at 40° C. for two hours. The reaction solution was treated with an aqueous solution of sodium carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated in vacuo and the residue was purified with silica gel column chromatography (ethyl acetate:n-hexane=5:1) to give 1-(5-bromo-3-methylpyridin-2-yl)-4-oxocyclohexanecarbonitrile (17.1 g).

Quelle