反应详情

A suspension of 8.30 g of N-phenylthiophthalimide in 75 ml of dry benzene at room temperature under nitrogen is treated with 6.58 g of tri-n-butylphosphine. After 15 minutes a dark orange solution is obtained and 4.78 g of cis-1-methyl-3-phenyl-4-piperidinol of Example 22 are added all at once. After 5 minutes the solid dissolves. After stirring for 24 hours at room temperature, the resultant suspension is filtered and the solid is washed well with hexane. The filtrate is concentrated in vacuo to an oil which is triturated for 18 hours with 250 ml of hexane. The undissolved material is filtered off, triturated with another 100 ml of hexane, and discarded. The filtrate is washed with water and then saturated aqueous NaCl solution and concentrated in vacuo to an oil. This material is dissolved in ether and extracted with 2 N HCl solution. The phases are separated and the ether phase is extracted with 2 N HCl solution. The combined acid extracts are washed with ether and then extracted with dichloromethane, keeping the two extracts separated. The first extract affords an oil which crystallizes upon standing for 18 hours. This material is triturated with petroleum ether and the solid is filtered and washed with petroleum ether until nearly colorless needles are obtained, m.p. s 51°, 55°-57° C. The filtrate is concentrated in vacuo to give an oil, which is combined with the oil obtained from the second dichloromethane extract and chromatographed on silica gel, using acetone as solvent. Another portion of purified free base is obtained as an oil which crystallizes rapidly on standing. The hydrochloride salts prepared by dissolving the free base in 250 ml of ether, filtering and treating the filtrate with HCl-saturated ether solution until acidic to wet pH paper. The resulting colorless solid is filtered, washed with ether and dried to afford a colorless salt, mp s 180°, 182°-184° C. This material is recrystallized by dissolving in a boiling mixture of 200 ml of ethylacetate and 150 ml of acetone, filtering hot and boiling down the filtrate to obtain crystalline needles of trans-1-methyl-3-phenyl-4-phenylthiopiperidine hydrochloride, mp s 167°, 168°-171° C.

1. customAfter 15 minutes a dark orange solution is obtained
2. dissolutionAfter 5 minutes the solid dissolves
3. filtrationthe resultant suspension is filtered
4. washthe solid is washed well with hexane
5. concentrationThe filtrate is concentrated in vacuo to an oil which
6. customis triturated for 18 hours with 250 ml of hexane
7. filtrationThe undissolved material is filtered off
8. customtriturated with another 100 ml of hexane
9. washThe filtrate is washed with water
10. concentrationsaturated aqueous NaCl solution and concentrated in vacuo to an oil
11. dissolutionThis material is dissolved in ether
12. extractionextracted with 2 N HCl solution
13. customThe phases are separated
14. extractionthe ether phase is extracted with 2 N HCl solution
15. washThe combined acid extracts are washed with ether
16. extractionextracted with dichloromethane
17. customseparated
18. extractionThe first extract
19. customaffords an oil which
20. customcrystallizes
21. waitupon standing for 18 hours
22. customThis material is triturated with petroleum ether
23. filtrationthe solid is filtered
24. washwashed with petroleum ether until nearly colorless needles
25. customare obtained
26. customs 51°, 55°-57° C
27. concentrationThe filtrate is concentrated in vacuo
28. customto give an oil, which
29. extractionextract
30. customchromatographed on silica gel
31. customAnother portion of purified free base is obtained as an oil which
32. customcrystallizes rapidly on standing
33. customThe hydrochloride salts prepared
34. filtrationfiltering
35. additiontreating the filtrate with HCl-saturated ether solution until acidic to wet pH paper
36. filtrationThe resulting colorless solid is filtered
37. washwashed with ether
38. customdried
39. customto afford a colorless salt, mp
40. customs 180°, 182°-184° C
41. customThis material is recrystallized
42. dissolutionby dissolving in a boiling mixture of 200 ml of ethylacetate and 150 ml of acetone
43. filtrationfiltering hot