反应详情

温度

3 °C

0.256 g (5.87 mmol) of sodium hydride (55%) is introduced into a thoroughly heated 100 ml three-necked round-bottomed flask, equipped with a magnetic stirrer, thermometer, dropping funnel and nitrogen delivery line, and washed twice with 5 ml of pentane. The pentane is removed using a pipette and the sodium hydride is blown dry with nitrogen. 20 ml of THF, rendered absolute using sodium, are then added, and the suspension is cooled to 3° C. by means of an ice bath with stirring. 0.68 g (5.87 mmol) of methyl acetoacetate dissolved in 5 ml of absolute THF is then slowly added dropwise so that the internal temperature does not exceed 5° C. The suspension is stirred for 15 min. while cooling with ice. 3.75 ml (6.0 mmol) of butyllithium (1.6M in hexane) are slowly added dropwise to the almost clear solution so that the internal temperature does not exceed 5° C. The clear yellow solution is stirred for 20 min. while cooling with ice. 1.0 g (3.55 mmol) of 3-(4-fluorophenyl)-1-isopropyl-1H-indole-2-carbaldehyde dissolved in 5 ml of absolute THF are added dropwise over a period of 2 min., in the course of which the internal temperature rises to 10° C. After 4 hours, the reaction mixture is poured into 100 ml of ice-water, stirred for 10 min. and extracted 3 times with 100 ml of ethyl acetate. The combined organic phases are washed twice with 100 ml of saturated sodium chloride solution in order to render neutral, dried over magnesium sulfate, filtered and concentrated by evaporation at 80° C.

1. customequipped with a magnetic stirrer
2. washnitrogen delivery line, and washed twice with 5 ml of pentane
3. customThe pentane is removed
4. dry with materialthe sodium hydride is blown dry with nitrogen
5. additionare then added
6. additionis then slowly added dropwise so that the internal temperature
7. customdoes not exceed 5° C
8. stirringThe suspension is stirred for 15 min.
9. temperaturewhile cooling with ice
10. customdoes not exceed 5° C
11. stirringThe clear yellow solution is stirred for 20 min.
12. temperaturewhile cooling with ice
13. additionare added dropwise over a period of 2 min., in the course of which the internal temperature
14. customrises to 10° C
15. stirringstirred for 10 min.
16. extractionextracted 3 times with 100 ml of ethyl acetate
17. washThe combined organic phases are washed twice with 100 ml of saturated sodium chloride solution in order
18. dry with materialdried over magnesium sulfate
19. filtrationfiltered
20. concentrationconcentrated by evaporation at 80° C.