The general procedure for the synthesis of N-Boc-azetidine-2-carboxylic acid from (S)-2-azetidinecarboxylic acid (10 g, 98.9 mmol), di-tert-butyl dicarbonate (28.06 g, 128.6 mmol), N-methylmorpholine (11.5 g, 113.7 mmol), and 1,4-dioxane (160 mL) was as follows: the above mixture was 0 °C for 4 hours, followed by continued stirring at room temperature for 18 hours. After completion of the reaction, the volatile solvent was removed by evaporation and the residue was dissolved in water and washed with dichloromethane (DCM). The aqueous layer was acidified to pH 1.0 with concentrated hydrochloric acid at 0 °C and subsequently extracted with DCM. The organic layer was dried with anhydrous sodium sulfate (Na2SO4) to give the final N-tert-butoxycarbonylazetidine-2-carboxylic acid (12.61 g, 63.1% yield) as an oily product. Its nuclear magnetic resonance hydrogen spectrum (NMR, CDCl3) data were as follows: δ 1.42 (s, 9H), 2.40 (m, 1H), 2.59 (m, 1H), 3.90 (m, 2H), 4.80 (t, 1H).
