Carbon Dioxide → 4-Piperidinopiperidine-1-carbonyl chloride

Temperature

0 °C

In 300 ml of methylene chloride, 20 ml (158 mmol) of trimethylsilyl chloride were dissolved. While the resulting solution was stirred under ice cooling in a nitrogen atmosphere, a solution of 22 g (131 mmol) of 4-piperidinopiperidine (1-1) dissolved in 100 ml of methylene chloride was gradually added dropwise over one hour. The resulting mixture was stirred at room temperature for one hour, whereby a solution containing 4-piperidinopiperidinyl trimethylsilyl (1-2) was obtained. While stirring the resulting solution, 5.9 liter (262 mmol) of a carbon dioxide gas of 1 atomic pressure were blown into the solution over two hours, whereby a solution containing 4-piperidinopiperidinyl trimethylsilyl carbamate derivative (1-3) was obtained. To the resulting solution, 11.5 ml (158 mmol) of thionyl chloride were added dropwise over 10 minutes under ice cooling and nitrogen atmosphere, followed by stirring at room temperature for 18 hours, whereby a solution containing 1-chlorocarbonyl-4-peridinopiperidine hydrochloride (1-4) was obtained. The solution was filtered and 8.8 g (33%) of 4-piperidinopiperidine hydrochloride were recovered as a residue. Under ice cooling, the filtrate was added to 330 ml of a 10% aqueous solution of sodium hydroxide. Then the organic layer obtained by separation was washed with water, dried over anhydrous magnesium sulfate and then concentrated under a low pressure. Isopropyl ether (50 ml) was added to the concentrate to dissolve the latter in the former, followed by cooling at 0° C. for 2 hours. The precipitate was then removed by filtration and the residue was concentrated under reduced pressure. The concentrate so obtained was recrystallized from 50 ml of n-hexane, whereby 15 g of the title compound (1-5) were obtained. The compound so obtained has the following physical properties:

1. additionwas gradually added dropwise over one hour
2. stirringThe resulting mixture was stirred at room temperature for one hour
3. customwas obtained
4. customwas obtained
5. stirringby stirring at room temperature for 18 hours
6. customwas obtained
7. filtrationThe solution was filtered
8. custom8.8 g (33%) of 4-piperidinopiperidine hydrochloride were recovered as a residue
9. additionUnder ice cooling, the filtrate was added to 330 ml of a 10% aqueous solution of sodium hydroxide
10. customThen the organic layer obtained by separation
11. washwas washed with water
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated under a low pressure
14. additionIsopropyl ether (50 ml) was added to the
15. concentrationconcentrate
16. dissolutionto dissolve the latter in the former,
17. customThe precipitate was then removed by filtration
18. concentrationthe residue was concentrated under reduced pressure
19. concentrationThe concentrate
20. customso obtained
21. customwas recrystallized from 50 ml of n-hexane

ORD record

ord-487daf8025714f04931b42ce121cb1e9

Source dataset

uspto-grants-2000_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06147215