反应详情

A solution of 4.79 g of diethyl azodicarboxylate in 125 ml of benzene is added, over a 90 minute period and at 5° C. under a nitrogen atmosphere, to a mixture of 4.72 g of cis-1-methyl-3-phenyl-4-piperidinol, 7.21 g of triphenylphosphine, 3.08 g of 3-fluorophenol and 125 ml of dry benzene. After stirring 18 hours at room temperature, the solid is filtered off and washed well with hexane. The filtrate is concentrated in vacuo to an oil, which is stirred 18 hours with hexane. The resulting mixture is filtered, and the resultant gummy solid is washed well with hexane. The filtrate is concentrated in vacuo to an oil which is taken up in ether and extracted with 2 N HCl solution. The acid extracts are then extracted with dichloromethane. The dichloromethane extracts are washed with 10% by weight aqueous NaOH solution, then with saturated aqueous NaCl solution, dried over Na2SO4, and concentrated to afford an oil. This material is chromatographed on silica gel, using acetone as solvent. An oil is thus obtained, which is taken up in ether and treated dropwise with a solution of 1.55 g of fumaric acid in a mixture of 100 ml of ether and 50 ml of absolute ethanol. The solvent is removed in vacuo and the resulting gum is triturated to a solid with ether. The solid is filtered, washed with ether, and dried to afford a solid, mp s 160°, 161°-164° C. Recrystallization from ethyl acetate and then from a mixture of ethyl acetate and acetone affords trans-4-(3-fluorophenoxy)1-methyl-3-phenylpiperidine fumarate, mp s 155°, 156.5°-158° C.

1. filtrationthe solid is filtered off
2. washwashed well with hexane
3. concentrationThe filtrate is concentrated in vacuo to an oil, which
4. stirringis stirred 18 hours with hexane
5. filtrationThe resulting mixture is filtered
6. washthe resultant gummy solid is washed well with hexane
7. concentrationThe filtrate is concentrated in vacuo to an oil which
8. extractionextracted with 2 N HCl solution
9. extractionThe acid extracts are then extracted with dichloromethane
10. washThe dichloromethane extracts are washed with 10% by weight aqueous NaOH solution
11. dry with materialwith saturated aqueous NaCl solution, dried over Na2SO4
12. concentrationconcentrated
13. customto afford an oil
14. customThis material is chromatographed on silica gel
15. customAn oil is thus obtained
16. customThe solvent is removed in vacuo
17. customthe resulting gum is triturated to a solid with ether
18. filtrationThe solid is filtered
19. washwashed with ether
20. customdried
21. customto afford a solid, mp
22. customs 160°, 161°-164° C
23. customRecrystallization from ethyl acetate
24. additionfrom a mixture of ethyl acetate and acetone