反应详情

温度

0 °C

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)+.

1. stirringstirred at room temperature for 1 hour
2. stirringadditionally stirred for 1 hour
3. extractionextracted with ethyl acetate
4. washwashed with saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. customthe solvent was evaporated in vacuo
7. additionTo the residue were added water (10 ml) and trifluoroacetic acid (50 ml)
8. stirringstirred at room temperature for 6 hours
9. additionThe reaction solution was added to an aqueous solution of potassium carbonate
10. extractionthe mixture was extracted with ethyl acetate
11. washthe organic layer was washed with saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. customthe solvent was evaporated in vacuo
14. customThe residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)