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 reaction mixture stirred for 1 h. The solvents were evaporated and the resulting residue was stirred with 400 mL THF and 400 mL 2 M HCl for 1 h. The mixture was concentrated to remove organics and was then 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 solvents were evaporated
6. stirringthe resulting residue was stirred with 400 mL THF and 400 mL 2 M HCl for 1 h
7. concentrationThe mixture was concentrated
8. customto remove organics
9. extractionwas then extracted with ether (3×300 mL)
10. extractionextracted with ethyl acetate
11. washThe organic layer was washed with water and brine
12. dry with materialdried over anhydrous sodium sulfate
13. customthe solvent evaporated

ORD record

ord-63b8a2700e1540b4b843592293578346

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07259157B2