General procedure for the synthesis of tert-butyl 4-(2-aminopropan-2-yl)piperidine-1-carboxylate from methyllithium and N-Boc-4-cyanopiperidine: firstly, cerium(III) chloride heptahydrate (25.5 g, 68.4 mmol) powder was stirred at 145 °C for 18 h under vacuum (<0.1 mmHg). After the solid was cooled to room temperature, THF (120 mL) was added and stirred at room temperature for 2 hours. Subsequently, the suspension was cooled to -78 °C and methyl lithium (45 mL, 1.4 M, dissolved in ether, 63 mmol) was added dropwise over 30 min. The reaction mixture was continued to be stirred at -78 °C for 30 min. A solution of 1-(tert-butoxycarbonyl)-4-cyanopiperidine (4.35 g, 20.7 mmol) in THF (15 mL) was slowly added via cannula, and the reaction was carried out at -78 °C for 4.5 hours. Upon completion of the reaction, ammonium hydroxide (40 mL) was added and the reaction mixture was slowly warmed to room temperature. After addition of dichloromethane (100 mL), the mixture was stirred at room temperature for 1 hour and then filtered through Celite. The Celite pad was washed with dichloromethane (3 x 50 mL). After combining the filtrates, the target product tert-butyl 4-(2-aminopropan-2-yl)piperidine-1-carboxylate was concentrated under reduced pressure to give tert-butyl 4-(2-aminopropan-2-yl)piperidine-1-carboxylate (5.0 g, 99% yield).
