反应详情

0.465 g (10.65 mmol) of sodium hydride (55%) are introduced into a 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. 10 ml of THF, rendered absolute using sodium, are added, and 1.84 g (7.46 mmol) of diethyl (N-methoxy-N-methylcarbamoyl-methyl)phosphonate dissolved in 5 ml of THF are slowly added dropwise so that the temperature does not exceed 30° C. 1 g (3.55 mmol) of 3-(4-fluorophenyl)-1-isopropyl-1H-indole-2-carbaldehyde dissolved in 10 ml of THF is then added dropwise and the clear, slightly yellow solution is stirred overnight. The reaction mixture is poured into 100 ml of water and extracted 3 times with 50 ml of ethyl acetate. The combined organic phases are washed twice with 50 ml of saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated by evaporation. Flash chromatography (hexane/ethyl acetate=2:1) and crystallisation from 94% ethanol yields slightly yellow crystals having a melting point of from 123 to 124° C.

1. customround-bottomed flask, equipped 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 added
6. additionare slowly added dropwise so that the temperature
7. customdoes not exceed 30° C
8. additionis then added dropwise
9. extractionextracted 3 times with 50 ml of ethyl acetate
10. washThe combined organic phases are washed twice with 50 ml of saturated sodium chloride solution
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated by evaporation
14. customFlash chromatography (hexane/ethyl acetate=2:1) and crystallisation from 94% ethanol
15. customyields slightly yellow crystals
16. customof from 123 to 124° C.