Benzaldehyde → 4-Aminomethyl-1-N-Cbz-piperidine

4-Aminomethylpiperidine (40 g, 350 mmol) and benzaldehyde (37.3 mL, 368 mmol) in toluene (600 mL) were heated to reflux under Dean Stark conditions for 2 h. The resulting reaction mixture was cooled to room temperature and 500 mL dichloromethane was added. The resulting solution was cooled to 5° C. and treated with N-(benzyloxycarbonyloxy)succinimide (91.7 g, 368 mmol). After 10 min, the cooling bath was removed and the resulting reaction mixture stirred for 1 h. The solvents were evaporated and the residue stirred with 400 mL THF and 400 mL 2M HCl for 1 h. The mixture was concentrated to remove organics and extracted with ether (3×300 mL). The aqueous phase was adjusted to pH14 with 50% NaOH and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and the solvent evaporated to give benzyl 4-(aminomethyl)piperidine-1-carboxylate as an oil.

1. temperatureto reflux under Dean Stark conditions for 2 h
2. customThe resulting reaction mixture
3. temperatureThe resulting solution was cooled to 5° C.
4. customthe cooling bath was removed
5. customthe resulting reaction mixture
6. customThe solvents were evaporated
7. stirringthe residue stirred with 400 mL THF and 400 mL 2M HCl for 1 h
8. concentrationThe mixture was concentrated
9. customto remove organics
10. extractionextracted with ether (3×300 mL)
11. extractionextracted with ethyl acetate
12. washThe organic layer was washed with water and brine
13. dry with materialdried over anhydrous sodium sulfate
14. customthe solvent evaporated

ORD record

ord-f2a0c81727b44c73ba1cc626d63bb9c9

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07053089B2