反应详情

101.66 g of methyl 1-(tert-butyloxycarbonyl)-4-oxopiperidine-3-carboxylate were added, under an inert atmosphere and at a temperature close to 20° C., to 2.156 liters of a saturated aqueous solution of ammonium chloride and of THF (10/1 by volume) of THF. 34.73-cm3 of allyl bromide were then added, followed by 77.51 g of zinc while maintaining the temperature below 30° C. A solution of 69.47-cm3 of allyl bromide in 50-cm3 of THF was then poured in dropwise. After stirring for 3 hours at a temperature close to 20° C., the reaction was incomplete. 77.51 g of zinc were again added and then 104-cm3of allyl bromide were poured in dropwise while the temperature was maintained below 30° C. The stirring was maintained at a temperature close to 20° C. for 15 hours, after which the reaction was still incomplete. 35 g of zinc were again added and then 55-cm3 of allyl bromide were poured in dropwise while the temperature was maintained below 30° C. The stirring was maintained at a temperature close to 20° C. for 4 hours, after whichthe reaction was still incomplete. 10 g of zinc were again added and then 25-cm3 of allyl bromide were poured in dropwise while the temperature was maintained below 30° C. The stirring was maintained at a temperature close to 20° C. for 2 hours. The reaction mixture was taken up in 900-cm3 of a 1 N HCl solution and 2 liters of ethyl ether and filtered on sintered glass. The filtrate was washed with 3 times 500-cm3 of etyl ether. The organic phase was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and concentrated to dryness under reduced pressure (5 kPa). A yellow oil was obtained, which was purified by chromatography, under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45 μ; diameter 12 cm; height 60 cm), eluting with a mixture of cyclohexane-ethyl acetate (80/20 by volume) and collecting 200-cm3 fractions. Fractions 51 to 75 were combined and then concentrated. 63.5 g of methyl 1-(tert-butyloxycarbonyl)-4-allyl-4-hydroxypiperidine-3-carboxylate were obtained in the form of a light yellow oil.

1. temperaturewhile maintaining the temperature below 30° C
2. customclose to 20° C.
3. temperaturewas maintained below 30° C
4. temperatureThe stirring was maintained at a temperature
5. customclose to 20° C. for 15 hours
6. temperaturewas maintained below 30° C
7. temperatureThe stirring was maintained at a temperature
8. customclose to 20° C. for 4 hours
9. temperaturewas maintained below 30° C
10. temperatureThe stirring was maintained at a temperature
11. customclose to 20° C. for 2 hours
12. filtrationfiltered on sintered glass
13. washThe filtrate was washed with 3 times 500-cm3 of etyl ether
14. washThe organic phase was washed with a saturated aqueous sodium chloride solution
15. dry with materialdried over magnesium sulfate
16. concentrationconcentrated to dryness under reduced pressure (5 kPa)
17. customA yellow oil was obtained
18. customwhich was purified by chromatography, under a nitrogen pressure of 50 kPa
19. washon a column of silica gel (particle size 20-45 μ; diameter 12 cm; height 60 cm), eluting with a mixture of cyclohexane-ethyl acetate (80/20 by volume)
20. customcollecting 200-cm3 fractions
21. concentrationconcentrated