反应详情

温度

6 °C

A mixture of 4.78 g of cis-1-methyl-3-phenyl-4-piperidinol of Example 22, 7.21 g of triphenylphosphine, 2.97 g of p-cresol and 125 ml of anhydrous benzene is cooled to 6° C. and a solution of 4.79 g of diethyl azodicarboxylate in 125 ml of benzene is added dropwise under nitrogen over a 90-minute period. The temperature is allowed to rise gradually so that at completion of the addition it is 22° C. After stirring for 18 hours at room temperature, the suspended solid is filtered off, washed with hexane, and the filtrate concentrated in vacuo to an oil. This material is triturated with 200 ml of hexane for 90 minutes, the liquid is decanted, and the solid triturated for a few minutes with another 200 ml of hexane. Concentration in vacuo of the hexane extracts affords an oil, which is dissolved in 250 ml of dichloromethane and extracted with 2 N HCl solution. The dichloromethane phase is washed successively with 10% aqueous NaOH solution, water, and saturated aqueous NaCl solution, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to a mixture of a solid and an oil. This mixture is triturated with hexane, filtered, and the filtrate is concentrated in vacuo to afford an oil. This oil is chromatographed on silica gel, using acetone and then 25% methanol/acetone as solvent. The fractions containing product are combined and concentrated in vacuo to an oil which is taken up in ether and filtered through a Celite pad. The filtrate affords an oil which is triturated with boiling hexane and filtered hot. The filtrate is cooled and the resultant precipitated solid is filtered off and the filtrate concentrated in vacuo to yield an oil. This oil is dissolved in 50 ml of ether and added dropwise to a solution of 1.36 g of maleic acid in 25 ml of ether. The resulting solid is filtered, washed with ether, and dried to afford crude salt, melting near 100° C. Recrystallization from ethyl acetate affords a solid of trans-1-methyl-3-phenyl-4-(4-tolyl)piperidine maleate, mp s 130°, 131°-132° C.

1. additionto rise gradually so that at completion of the addition it
2. customis 22° C
3. filtrationthe suspended solid is filtered off
4. washwashed with hexane
5. concentrationthe filtrate concentrated in vacuo to an oil
6. customThis material is triturated with 200 ml of hexane for 90 minutes
7. customthe liquid is decanted
8. customthe solid triturated for a few minutes with another 200 ml of hexane
9. concentrationConcentration in vacuo of the hexane
10. customextracts affords an oil, which
11. extractionextracted with 2 N HCl solution
12. washThe dichloromethane phase is washed successively with 10% aqueous NaOH solution, water, and saturated aqueous NaCl solution
13. dry with materialdried over anhydrous Na2SO4
14. filtrationfiltered
15. concentrationconcentrated in vacuo to a mixture of a solid
16. customThis mixture is triturated with hexane
17. filtrationfiltered
18. concentrationthe filtrate is concentrated in vacuo
19. customto afford an oil
20. customThis oil is chromatographed on silica gel
21. additionThe fractions containing product
22. concentrationconcentrated in vacuo to an oil which
23. filtrationfiltered through a Celite pad
24. customThe filtrate affords an oil which
25. customis triturated with boiling hexane
26. filtrationfiltered hot
27. temperatureThe filtrate is cooled
28. customthe resultant precipitated solid
29. filtrationis filtered off
30. concentrationthe filtrate concentrated in vacuo
31. customto yield an oil
32. filtrationThe resulting solid is filtered
33. washwashed with ether
34. customdried
35. customto afford crude salt
36. custommelting near 100° C
37. customRecrystallization from ethyl acetate