反应详情

A solution of 4.79 g of diethyl azodicarboxylate in 125 ml of benzene is added dropwise under a nitrogen atmosphere at 5°-10° C. over a 90 minute period to a mixture of 4.78 g of cis-1-methyl-3-phenyl-4-piperidinol, 7.21 g of triphenylphosphine, 3.08 g of 2-fluorophenol and 125 ml of dry benzene. After the addition, the mixture is stirred for 18 hours at room temperature, then filtered, and the solid waste is washed well with hexane. The filtrate is concentrated in vacuo to an oil which is stirred 18 hours with hexane. A gummy solid is filtered off, washed with hexane, and the filtrate concentrated in vacuo to an oil. This material is taken up in ether and extracted with 2 N HCl solution. The acid extracts are extracted with dichloromethane. The dichloromethane extracts are washed with 10% by weight of aqueous NaOH solution, then with saturated aqueous NaCl solution, dried over anhydrous Na2SO4, and concentrated in vacuo to afford and oil. The oil is chromatographed on silica gel, using acetone as solvent. A purified free base is obtained as an oil. This material is dissolved in 75 ml of ether and treated dropwise with a solution of 1.44 g of fumaric acid in a mixture of 25 ml of absolute ethanol and 50 ml of ether. Scratching of the resulting solution causes crystallization to occur. The solid is filtered, washed with ether, and dried to afford a colorless solid of trans-4-(2-fluorophenoxy)-1-methyl-3-phenylpiperidine furmarate hemihydrate, m.p. partially melts 149°, 161°-167° C. Recrystallization from ethyl acetate affords the product having mp s 154, 156° C., dec.

1. additionAfter the addition
2. filtrationfiltered
3. washthe solid waste is washed well with hexane
4. concentrationThe filtrate is concentrated in vacuo to an oil which
5. stirringis stirred 18 hours with hexane
6. filtrationA gummy solid is filtered off
7. washwashed with hexane
8. concentrationthe filtrate concentrated in vacuo to an oil
9. extractionextracted with 2 N HCl solution
10. extractionThe acid extracts are extracted with dichloromethane
11. washThe dichloromethane extracts are washed with 10% by weight of aqueous NaOH solution
12. dry with materialwith saturated aqueous NaCl solution, dried over anhydrous Na2SO4
13. concentrationconcentrated in vacuo
14. customto afford
15. customThe oil is chromatographed on silica gel
16. customA purified free base is obtained as an oil
17. customcrystallization
18. filtrationThe solid is filtered
19. washwashed with ether
20. customdried