反应详情

温度

0 °C

In 40 ml of anhydrous tetrahydrofuran, is dissolved 3.64 ml of diisopropylamine. The resulting solution is cooled to 0° C. After dropping 15.4 ml of 1.62M solution of n-butyllithium in n-hexane thereto and stirring the resulting mixture for 10 minutes at that temperature, it is cooled to -78° C. and stirred for 20 minutes. Then, 2.34 ml of ethyl acetate is dropped and stirred at that temperature for 30 minutes. Then, 160 ml of an anhydrous tetrahydrofuran solution containing 6.13 g of the 6-cyano-2,2-dimethyl-4-(1,2-dihydro-2-oxo-4-formyl-1-pyridinyl)-2H-benzo[b]pyran obtained in Example 25 is added at that temperature over a period of 55 minutes, and the whole mixture is reacted first at that temperature for one hour, then at 0° C. for 30 minutes and then at room temperature for 30 minutes. After stopping the reaction by adding 0.2M phosphate buffer, the reaction mixture is extracted with ethyl acetate. The organic layer is washed successively with 2N aqueous hydrochloric acid, water and saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The inorganic matter is filtered off, and the filtrate is concentrated under reduced pressure. The residue thus obtained is purified by silica gel column chromatography using 3/1 mixture of ethyl acetate/n-hexane as a developing solvent. Thus, 5.88 g of 6-cyano-2,2-dimethyl-4-{1,2-dihydro-2-oxo-4-(1-hydroxy-2- ethoxycarbonylethyl)- 1-pyridinyl}-2H-benzo[b]pyran is obtained.

1. temperatureis cooled to -78° C.
2. stirringstirred for 20 minutes
3. stirringstirred at that temperature for 30 minutes
4. additionis added at that temperature over a period of 55 minutes
5. customthe whole mixture is reacted first at that temperature for one hour
6. waitat 0° C. for 30 minutes
7. waitat room temperature for 30 minutes
8. customthe reaction
9. extractionthe reaction mixture is extracted with ethyl acetate
10. washThe organic layer is washed successively with 2N aqueous hydrochloric acid, water and saturated aqueous solution of sodium chloride
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationThe inorganic matter is filtered off
13. concentrationthe filtrate is concentrated under reduced pressure
14. customThe residue thus obtained
15. customis purified by silica gel column chromatography
16. addition3/1 mixture of ethyl acetate/n-hexane as a developing solvent