반응 #1835699

반응 방정식

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

수율 97.6%

용매

water

반응 조건

후처리

1. 1
   workup.STIRRINGstirred for 30 minutes
2. 2
   workup.STIRRINGfurther stirred at room temperature for an hour
3. 3
   추출extracted with ethyl acetate
4. 4
   세척The organic layer was washed with saturated brine
5. 5
   농축concentrated 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
   추출extracted with ethyl acetate
10. 10
    건조The organic layer was dried over anhydrous magnesium sulfate
11. 11
    농축concentrated in vacuo
12. 12
    기타the residue was purified with silica gel column chromatography (ethyl acetate:n-hexane=5:1)

실험 절차

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).

출처