In a 200 mL four-necked flask equipped with a stirrer, pH sensor, and two dropping funnels, 90 g of ethanol and 10.0 g (0.1 mol) of 3-aminopiperidine were added and stirred at 10 to 15 °C. 21.8 g (0.1 mol) di-tert-butyl dicarbonate was slowly added through one dropping funnel while 17.6 g (0.11 mol) 25% aqueous sodium hydroxide was added dropwise through the other dropping funnel, and the dropping rate was controlled to maintain the pH of the reaction system between 11.8 and 12.2. The titration process was completed in about 1 hour. Upon completion of the reaction, the composition of the reaction mixture was analyzed and confirmed to contain 6% unreacted 3-aminopiperidine, 91.5% of the target product 3-amino-1-tert-butoxycarbonylpiperidine and 1.1% of the by-product 3-tert-butoxycarbonylaminopiperidine.
