反应详情

A three neck 500 mL flask was charged with 20 g (0.23 mole) of piperidine, 53 g (0.47 mole) of 3-methylcyclohexanone and 200 mL of anhydrous cyclohexane. To the resulting solution, 84 g (0.70 mole) of anhydrous magnesium sulfate was added and the mixture was mechanically stirred and heated at reflux (the reaction was monitored by NMR) for 192 hours. The reaction mixture was then filtered through a fritted glass funnel. The filtrate (containing the enamine product, excess 3-methylcyclohexanone and cyclohexane) was transferred to a hydrogenation vessel. To this mixture, 3 g of 10% Pd on activated carbon was added and the vessel affixed to a hydrogenation Parr shaker at 65 psi of hydrogen. The mixture was left on the Parr shaker for 6 hours at room temperature. The mixture was then filtered through a bed of Celite® in a fitted glass filtering funnel. The filtrate was transferred to a round bottom flask and concentrated under reduced pressure on a rotary evaporator. The obtained residue, which contained 1-(3-methylcyclohexyl)piperidine and excess 3-methylcyclohexanone, was treated with 120 mL of 3M aqueous HCl solution. The mixture was stirred in an ice-water bath for 20 minutes. Then, the mixture was transferred to a reparatory funnel and extracted with 200 mL of diethyl ether. The ether layer, containing the excess 3-methylcyclohexanone, was separated from aqueous layer containing the amine in the form of its onium hydrochloride salt. The ether layer was dried over MgSO4, filtered and concentrated under reduced pressure on a rotary evaporator to recover 31 g of the excess 3-methylcyclohexanone. The aqueous layer was treated with 50 wt. % aqueous NaOH solution in an ice bath until a pH of about 11 was reached. This solution was then extracted with 300 mL of diethyl ether. The ether layer was dried over MgSO4, filtered and concentrated under reduced pressure on a rotary evaporator to give 32 g of 1-(3-methylcyclohexyl)piperidine as a yellow oil. The product was confirmed by 1H-NMR and 13C-NMR analysis. Some piperidine was also present in the oil as an impurity.

1. temperatureheated
2. temperatureat reflux (the reaction
3. customfor 192 hours
4. filtrationThe reaction mixture was then filtered through a fritted glass funnel
5. additionThe filtrate (containing the enamine product, excess 3-methylcyclohexanone and cyclohexane)
6. customwas transferred to a hydrogenation vessel
7. additionTo this mixture, 3 g of 10% Pd on activated carbon was added
8. filtrationThe mixture was then filtered through a bed of Celite® in a fitted glass
9. filtrationfiltering funnel
10. customThe filtrate was transferred to a round bottom flask
11. concentrationconcentrated under reduced pressure on a rotary evaporator
12. additionwas treated with 120 mL of 3M aqueous HCl solution
13. stirringThe mixture was stirred in an ice-water bath for 20 minutes
14. customThen, the mixture was transferred to a reparatory funnel
15. extractionextracted with 200 mL of diethyl ether
16. additionThe ether layer, containing the excess 3-methylcyclohexanone
17. customwas separated from aqueous layer
18. additioncontaining the amine in the form of its onium hydrochloride salt
19. dry with materialThe ether layer was dried over MgSO4
20. filtrationfiltered
21. concentrationconcentrated under reduced pressure on a rotary evaporator
22. customto recover 31 g of the excess 3-methylcyclohexanone
23. additionThe aqueous layer was treated with 50 wt. % aqueous NaOH solution in an ice bath until a pH of about 11
24. extractionThis solution was then extracted with 300 mL of diethyl ether
25. dry with materialThe ether layer was dried over MgSO4
26. filtrationfiltered
27. concentrationconcentrated under reduced pressure on a rotary evaporator