The general procedure for the synthesis of 1-BOC-piperidine-3-carboxylic acid from di-tert-butyl dicarbonate and 3-piperidinecarboxylic acid is as follows:1. Dissolve piperidine-3-carboxylic acid (50.0 g, 387.5 mmol) in tert-butyl alcohol (464.0 mL) at 0 °C, slowly add 1N NaOH solution (464.0 mL), and stir for 10 min. 2. Add di-tert-butyl dicarbonate (Boc-anhydride, 143.6 g, 659.0 mmol) to the above solution. 3. Stir the reaction mixture for 12 hours at room temperature. 4. Di-tert-butyl carbonate (Boc-anhydride, 143.6 g, 659.0 mmol) was added to the above solution. 3. The reaction mixture was stirred at room temperature for 12 h. 4. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, and then neutralized to pH neutral with 1N HCl solution. 5. The precipitated white solid was collected by filtration, and dried to give 1-BOC-piperidine-3-carboxylic acid (1 , 86.0 g, yield 97%). The product was characterized by 1H NMR (400 MHz, DMSO-d6), δ 1.38 (s, 9H), 1.47 (m, 1H), 1.59 (dt, J = 3.8 Hz, 1H), 1.87 (m, 1H), 2.28 (m, 1H), 2.77-2.84 (dt, J = 2.5,3.0 Hz, 1H), 3.0 (brs. 1H), 3.67 (d, J = 11.0 Hz, 1H), 3.87 (brs, 1H), 12.2 (s, 1H).
