Step 1: Synthesis of tert-butyl 4-bromopiperidine-1-carboxylate
To a 35 mL dichloromethane suspension containing 5 g (0.02 mol) of 4-bromopiperidine hydrobromide, 7.09 mL (0.04 mol) of N,N-diisopropylethylamine was added slowly and dropwise at 0 °C. The reaction mixture was stirred for 30 minutes and then continued with the dropwise addition of 6.67 g (0.031 mol) of di-tert-butyl dicarbonate to a 35 mL dichloromethane solution. The reaction mixture was stirred at room temperature for 18 hours. Upon completion of the reaction, the reaction mixture was washed sequentially with 1 M aqueous hydrochloric acid (2 x 30 mL) and brine (30 mL). The organic layer was separated, dried with anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to give 6.9 g of 4-bromopiperidine-1-carboxylic acid tert-butyl ester as a yellow oil in quantitative yield. The product was characterized by 1H NMR (250 MHz, chloroform-d): δ 1.46 (9H, s), 1.79-2.00 (2H, m), 2.00-2.16 (2H, m), 3.31 (2H, ddd, J = 13.67,7.73,3.73 Hz), 3.68 (2H, ddd, J = 13.55,6.85,3.65 Hz), 4.34 (1H, tt, J = 7.69,3.81 Hz).
