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 reaction mixture was cooled to room temperature and 500 mL dichloromethane added. The 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 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 compound.

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

ORD record

ord-a69be3f99de4436bb1c42b61389e6007

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07053089B2