Benzaldehyde → 4-Amino-1-Boc-piperidine

Participants

Reaction Steps

To a solution of 50 g (262.8 mM) of 4-amino-1-benzylpiperidine in 500 ml of methanol was added 5 g of 5% palladium-on-carbon (hydrous) and catalytic reduction was carried out at the hydrogen pressure of 5 kg/cm2 at 35° C. for 15 hours. The catalyst Pd/carbon was then filtered off and the filtrate was concentrated under reduced pressure to provide 4-aminopiperidine. To a solution of this 4-aminopiperidine in toluene (500 ml) was added 27.89 g (262.8 mM) of benzaldehyde and the mixture was refluxed for 3 hours, with the byproduct water being removed with a Dean-Stark trap. After cooling to room temperature, 63.08 g (289 mM) of di-tert-butyl dicarbonate was added dropwise gradually over about 1 hour and the mixture was stirred at room temperature overnight. After the solvent was distilled off under reduced pressure, 290 ml of 1N-aqueous solution of potassium hydrogen sulfate was added to the residue at room temperature and the mixture was stirred for 2 hours. The resulting crystal crop was harvested by filtration and rinsed with water, ethanol, and diethyl ether to provide tert-butyl 4-aminopiperidine-1-carboxylate ½ potassium hydrogen sulfate salt as colorless crystals (49.02 g, 71%).

Provenance & Evidence