Benzyl chloroformate → Benzyl 4-(aminomethyl)piperidine-1-carboxylate--hydrogen chloride (1/1)

To a solution of 4-aminomethyl piperidine (7.19 g) in anhydrous methylene chloride (80 ml), there was dropwise added a solution of benzyloxycarbonyl chloride (3.0 ml) in anhydrous methylene chloride (25 ml) under a nitrogen gas atmosphere while cooling with dry ice-methanol. After the completion of the dropwise addition, the resulting mixture was stirred while cooling with dry ice-methanol for 20 minutes and then stirred at room temperature for additional 2 hours. The reaction solution was concentrated under reduced pressure and ether and a citric acid solution were added to the resulting residue. The resulting aqueous phase was washed twice with ether. After addition of chloroform to the aqueous phase, sodium carbonate was added thereto at room temperature with stirring to make the aqueous phase basic. Separately, the resulting organic phase was washed with saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting oily product was dissolved in ether and a 4N hydrogen chloride solution in ethyl acetate (10 ml) was added to the ether solution with ice cooling. The resulting precipitates were filtered off to thus give the title compound (Reference Compound 4-1, 1.86 g) in the form of crystals.

1. additionAfter the completion of the dropwise addition
2. stirringstirred at room temperature for additional 2 hours
3. concentrationThe reaction solution was concentrated under reduced pressure and ether
4. additiona citric acid solution were added to the resulting residue
5. washThe resulting aqueous phase was washed twice with ether
6. additionAfter addition of chloroform to the aqueous phase, sodium carbonate
7. additionwas added
8. stirringat room temperature with stirring
9. washSeparately, the resulting organic phase was washed with saturated sodium chloride aqueous solution
10. dry with materialdried over anhydrous magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. dissolutionThe resulting oily product was dissolved in ether
13. additiona 4N hydrogen chloride solution in ethyl acetate (10 ml) was added to the ether solution with ice cooling
14. customThe resulting precipitates
15. filtrationwere filtered off

ORD record

ord-415e247152f4454eaa969595d8784117

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06534499B2