反应详情

温度

45 °C

To a solution of 2j from Example 5 (2 g, 9.3 mmol) in dry N-methyl-2-pyrrolidone (20 ml) is added sodium hydride (0.37 g of a 60% dispersion in mineral oil) in portions at 0° C. under nitrogen. The mixture is stirred for 1 hour, the last 30 min. at room-temperature. 1c from Example 1 (2.67 g, 10 mmol) is added and the temperature is raised to 40-50° C. over night. After cooling the mixture is poured into water (100 ml) and extracted with dichloromethane. The organic phase is extracted with 4M hydrochloric acid. The acidic extract is cooled in ice, rendered alkaline by addition of sodium hydroxide (12M) and extracted with dichloromethane. The organic phase is dried over magnesium sulfate and evaporated to dryness. The residue is extracted with a mixture of dichloromethane and diethyl ether (1:1). This extract is concentrated under reduced pressure and the residue is dissolved in dimethoxyethane (60 ml). Aqueous sodium hydroxide (28 ml, 1 M) is added and the mixture is stirred at ambient temperature over night. The mixture is poured into water (200 ml) and a small volume of ethanol is added with stirring. The product is filtered off, washed with water and dried to leave 6j (2 g, 51%). Mp 135-136° C.

1. customthe last 30 min.
2. temperatureAfter cooling the mixture
3. extractionextracted with dichloromethane
4. extractionThe organic phase is extracted with 4M hydrochloric acid
5. extractionThe acidic extract
6. temperatureis cooled in ice
7. additionby addition of sodium hydroxide (12M)
8. extractionextracted with dichloromethane
9. dry with materialThe organic phase is dried over magnesium sulfate
10. customevaporated to dryness
11. extractionThe residue is extracted with a mixture of dichloromethane and diethyl ether (1:1)
12. concentrationThis extract is concentrated under reduced pressure
13. dissolutionthe residue is dissolved in dimethoxyethane (60 ml)
14. additionAqueous sodium hydroxide (28 ml, 1 M) is added
15. stirringthe mixture is stirred at ambient temperature over night
16. additionThe mixture is poured into water (200 ml)
17. additiona small volume of ethanol is added
18. stirringwith stirring
19. filtrationThe product is filtered off
20. washwashed with water
21. customdried