反应详情

3,3-Dimethyl-1-(2-hydroxyethyl)-1,3-dihydro-2H-indol-2-one (2.05 g, 10 mmol) and triethylamine (1.1 g, 10.9 mmol) was dissolved in dichloromethane under nitrogen and cooled to less than 5° C. in an ice/water bath. Methanesulfonyl chloride (1.3 g, 11.3 mmol) was added and the mixture was stirred for one hour with cooling. The mixture was washed with cold dilute hydrochloric acid, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting oil was dissolved in dry acetonitrile, 4-fluorobenzoylpiperidine para toluenesulfonate (Acros, 2.83 g, 11.7 mmol) potassium carbonate (3 g, 21.7 mmol) and potassium iodide (0.15 g, 0.9 mmol) were added. The mixture was stirred vigorously and heated under gentle reflux for two days. The mixture was poured into chloroform, washed with water, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting oil was taken up in 5N hydrochloric acid whereupon a white solid separated. This solid was recrystallised from ethanol to give 3,3-dimethyl-1-{2-[4-(4-fluorobenzoyl)-1-piperidinyl]-1-ethyl}-1,3-dihydro-2H-indol-2-one monohydrochloride. Melting point 236°-8° C.

1. temperaturecooled to less than 5° C. in an ice/water bath
2. temperaturewith cooling
3. washThe mixture was washed with cold dilute hydrochloric acid
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. dissolutionThe resulting oil was dissolved in dry acetonitrile
8. stirringThe mixture was stirred vigorously
9. temperatureheated
10. temperatureunder gentle reflux for two days
11. washwashed with water
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customseparated
16. customThis solid was recrystallised from ethanol