反应详情

温度

80 °C

0.96 g (9 mmol) of sodium carbonate, 1.35 g (9 mmol) of sodium iodide and 2.1 g (9 mmol) of 2-(3-chloropropyl)-2-cyclohexyl-1,3-dioxolane were added to a solution of 1.7 g (8.3 mmol) of 2,5-dimethyl-3-(4-hydroxyphenyl)piperidine in 10 ml of dimethylformamide and the resulting reaction mixture was stirred at a temperature of 80° C. for 16 hours. After cooling, the reaction mixture was poured on ice and extracted three times with ethyl acetate. After evaporating the organic layer under reduced pressure, the residue was dissolved in a mixture of 20 ml of dimethylformamide and 40 ml of 2N hydrochloric acid and stirred for 1 hour so as to split the dioxolane group present. The solution was then extracted three times with diethyl ether, rendered basic by the addition of concentrated ammonia and extracted three times with ethyl acetate. The resulting organic layer was washed three times with water and once with a concentrated saline solution, dried on sodium sulphate an evaporated under reduced pressure. The resulting crude product (2.3 g) was purified by means of flash chromatography over 75 g of silicagel (Merck, grain size 0.040-0.063 mm) using a mixture of dichloromethane, methanol and concentrated ammonia (95:4.5:0.5) as an eluent. After combining and evaporating the desired fractions, totally 1.2 g (46%) of 1-(4-cyclohexyl-4 -oxobutyl)-2,5-dimethyl-3-(4-hydroxyphenyl)piperidine were obtained (compound no. 1).

1. customthe resulting reaction mixture
2. temperatureAfter cooling
3. additionthe reaction mixture was poured on ice
4. extractionextracted three times with ethyl acetate
5. customAfter evaporating the organic layer under reduced pressure
6. dissolutionthe residue was dissolved in a mixture of 20 ml of dimethylformamide and 40 ml of 2N hydrochloric acid
7. stirringstirred for 1 hour so as
8. customto split the dioxolane group present
9. extractionThe solution was then extracted three times with diethyl ether
10. additionrendered basic by the addition of concentrated ammonia
11. extractionextracted three times with ethyl acetate
12. washThe resulting organic layer was washed three times with water
13. customonce with a concentrated saline solution, dried on sodium sulphate
14. customan evaporated under reduced pressure
15. customThe resulting crude product (2.3 g) was purified by means of flash chromatography over 75 g of silicagel (Merck, grain size 0.040-0.063 mm)
16. additiona mixture of dichloromethane, methanol and concentrated ammonia (95:4.5:0.5) as an eluent
17. customevaporating the desired fractions