反应详情

2 g of (+)-5-ethoxycarbonyl-1-ethoxymethyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3-carboxylic acid are dissolved in 25 ml of acetone, and 1.5 g of finely powdered potassium carbonate, 7.5 ml of 1,3-dibromopropane and a spatula tip of [18]crown-6 are added. The mixture is stirred vigorously for 20 h at room temperature, after which the solution is filtered off from the solid, the filtrate is evaporated in vacuo and the excess 1,3-dibromopropane is distilled off under high vacuum. 15 ml of concentrated formic acid are added to the residue while cooling with ice; stirring is then carried out at room temperature until a clear solution has formed (about 15-20 minutes). The formic acid is distilled off in vacuo, the residue is dissolved in 30 ml of dichloromethane and the solution is washed with sodium bicarbonate solution and water, dried over sodium sulphate and evaporated again. The crystalline residue is triturated with diisopropyl ether, filtered off under suction, washed with diisopropyl ether and dried. 2.2 g are obtained and are heated at the boil, without further purification, with 1.32 g of 4,4-diphenylpiperidine hydrochloride and 2 g of potassium carbonate in a mixture of 20 ml of toluene and 4 ml of water for 30 h. After cooling, the phases are separated. The organic phase is washed twice with water and evaporated. The residue is chromatographed over a silica gel column using 95:5 chloroform/ethanol as the mobile phase. The chromatographically pure fractions are collected and evaporated. The residue is dissolved in dichloromethane, 2 ml of a saturated solution of hydrogen chloride in ether are added and the mixture is immediately evaporated in vacuo. Two portions of 20 ml of dichloromethane are distilled off, after which the residue is triturated with ether, filtered off under suction and dried. 2.65 g of the title compound which decomposes from 142° C. and has [α]22D =+18.9° (c=1, methanol) are obtained.

1. filtrationafter which the solution is filtered off from the solid
2. customthe filtrate is evaporated in vacuo
3. distillationthe excess 1,3-dibromopropane is distilled off under high vacuum
4. addition15 ml of concentrated formic acid are added to the residue
5. temperaturewhile cooling with ice
6. stirringstirring
7. customis then carried out at room temperature until a clear solution
8. customhas formed (about 15-20 minutes)
9. distillationThe formic acid is distilled off in vacuo
10. dissolutionthe residue is dissolved in 30 ml of dichloromethane
11. washthe solution is washed with sodium bicarbonate solution and water
12. dry with materialdried over sodium sulphate
13. customevaporated again
14. customThe crystalline residue is triturated with diisopropyl ether
15. filtrationfiltered off under suction
16. washwashed with diisopropyl ether
17. customdried
18. custom2.2 g are obtained
19. temperatureAfter cooling
20. customthe phases are separated
21. washThe organic phase is washed twice with water
22. customevaporated
23. customThe residue is chromatographed over a silica gel column
24. customThe chromatographically pure fractions are collected
25. customevaporated
26. dissolutionThe residue is dissolved in dichloromethane
27. addition2 ml of a saturated solution of hydrogen chloride in ether are added
28. customthe mixture is immediately evaporated in vacuo
29. distillationTwo portions of 20 ml of dichloromethane are distilled off
30. customafter which the residue is triturated with ether
31. filtrationfiltered off under suction
32. customdried
33. customdecomposes from 142° C.
34. custom[α]22D =+18.9° (c=1, methanol)
35. customare obtained