To a 1:1 dioxane/water (60 mL) solution of 1-aminocyclopentanecarboxylic acid (3.0 g, 23.2 mmol) was slowly added sodium carbonate (Na2CO3, 12.3 g, 116 mmol), followed by dropwise addition of benzyl chloroformate (3.6 mL, 25.5 mmol). The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the pH was carefully adjusted to 2 with 1 M hydrochloric acid (HCl) and then extracted with ethyl acetate (EtOAc, 3 × 30 mL). The organic phases were combined, washed with saturated saline (30 mL), dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to give a light yellow oily crude product. The crude product was analyzed by LCMS and NMR as a mixture of Cbz-cycloleucine and its corresponding benzyl ester. The crude product was dissolved in 1:1 tetrahydrofuran/water (THF/H2O, 60 mL) and lithium hydroxide (LiOH, 2.67 g, 116 mmol) was added. The mixture was stirred overnight at room temperature and then washed with ether (Et2O, 3 × 30 mL), then acidified with 1 M HCl to pH = 2 and finally extracted with EtOAc (3 × 30 mL). The organic phases were combined, washed with saturated saline (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give Cbz-cycloleucine (4.76 g, 78% yield).LCMS: m/z 264 [M + H]+.
