반응 #1835741

반응 방정식

sodium bis(trimethylsilyl)amide

5-bromo-2-fluoropyridine

1,4-dioxaspiro[4.5]decane-8-carbonitrile

potassium carbonate

→

1-(5-bromopyridin-2-yl)-4-oxocyclohexanecarbonitrile

수율 64.4%

용매

tetrahydrofuran

tetrahydrofuran

Tetrahydrofuran

반응 조건

후처리

1. 1
   workup.STIRRINGstirred at room temperature for 1 hour
2. 2
   workup.STIRRINGadditionally stirred for 1 hour
3. 3
   추출extracted with ethyl acetate
4. 4
   세척washed with saturated brine
5. 5
   건조dried over anhydrous sodium sulfate
6. 6
   기타the solvent was evaporated in vacuo
7. 7
   workup.ADDITIONTo the residue were added water (10 ml) and trifluoroacetic acid (50 ml)
8. 8
   workup.STIRRINGstirred at room temperature for 6 hours
9. 9
   workup.ADDITIONThe reaction solution was added to an aqueous solution of potassium carbonate
10. 10
    추출the mixture was extracted with ethyl acetate
11. 11
    세척the organic layer was washed with saturated brine
12. 12
    건조dried over anhydrous magnesium sulfate
13. 13
    기타the solvent was evaporated in vacuo
14. 14
    기타The residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)

실험 절차

To 1,4-dioxaspiro[4.5]decane-8-carbonitrile (13.4 g) described in Reference Example 82 (1) was added a 1 M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (100 ml), stirred at 0° C., then a solution of 5-bromo-2-fluoropyridine (12.8 g) in tetrahydrofuran (20 ml) was added thereto, and stirred at room temperature for 1 hour. Tetrahydrofuran (20 ml) was added thereto, additionally stirred for 1 hour, then to the reaction solution was added an aqueous solution of potassium carbonate, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and then the solvent was evaporated in vacuo. To the residue were added water (10 ml) and trifluoroacetic acid (50 ml), and stirred at room temperature for 6 hours. The reaction solution was added to an aqueous solution of potassium carbonate, the mixture was extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) to give 1-(5-bromopyridin-2-yl)-4-oxocyclohexanecarbonitrile (13.08 g) as a pale yellow solid. MS (ESI) m/z: 279, 281 (M+H)+.

출처