反应详情

A solution of 4.79 g of diethyl azodicarboxylate in 125 ml of anhydrous benzene is added dropwise at 4° C. under nitrogen over a 90 minute period to a mixture of 4.78 g of cis-1-methyl-3-phenyl-4-piperidinol of Example 1g, 7.21 g of triphenylphosphine, 3.54 g of 2-chlorophenol and 125 ml of anhydrous benzene. The mixture is stirred 18 hours at room temperature under nitrogen and then is filtered. The solid is washed well with hexane and the filtrate is concentrated in vacuo. The residue is triturated 18 hours with 250 ml of hexane and then filtered. The solid is washed well with hexane, triturated with ether and then filtered. The filtrates are combined and concentrated in vacuo to an oil. An ether solution of this material is made and is then extracted with 2 N HCl solution. The acid extracts are washed with ether, followed by extraction with dichloromethane. The dichloromethane extracts are washed with 10% aqueous NaOH solution, then with saturated NaCl solution, dried over anhydrous Na2SO4 and concentrated in vacuo to an oil. This material is chromatographed on silica gel, using acetone as a solvent to obtain an oil. This oil is dissolved in ether and treated dropwise with an HCl-saturated ether solution to yield a salt. The salt is filtered and washed with ether to afford a solid, mp s 230°, 232°-234° C. This material suspended in 25 ml of boiling ethyl acetate and acetone is gradually added to the boiling mixture until a solution is obtained. The solution is filtered hot and boiled down to start crystallization to yield a solid, mp 233°-235.5° C. of trans-4-(2-chlorophenoxy)-1-methyl-3-phenylpiperidine hydrochloride.

1. filtrationis filtered
2. washThe solid is washed well with hexane
3. concentrationthe filtrate is concentrated in vacuo
4. customThe residue is triturated 18 hours with 250 ml of hexane
5. filtrationfiltered
6. washThe solid is washed well with hexane
7. customtriturated with ether
8. filtrationfiltered
9. concentrationconcentrated in vacuo to an oil
10. extractionis then extracted with 2 N HCl solution
11. washThe acid extracts are washed with ether
12. extractionfollowed by extraction with dichloromethane
13. washThe dichloromethane extracts are washed with 10% aqueous NaOH solution
14. dry with materialwith saturated NaCl solution, dried over anhydrous Na2SO4
15. concentrationconcentrated in vacuo to an oil
16. customThis material is chromatographed on silica gel
17. customto obtain an oil
18. customto yield a salt
19. filtrationThe salt is filtered
20. washwashed with ether
21. customto afford a solid
22. custommp s 230°, 232°-234° C
23. customis obtained
24. filtrationThe solution is filtered hot
25. customcrystallization