General procedure for the synthesis of Fmoc-cycloleucine from 9-fluorenylmethyl-N-succinimidyl carbonate (Fmoc-OSu) and 1-aminocyclopentanecarboxylic acid: Fmoc-OSu (3.13 g, 9.3 mmol) was added to a mixture of acetonitrile/water (100 mL) and sodium bicarbonate (NaHCO3, 1.63 g, 1.4 mmol) containing 1-aminocyclopentanecarboxylic acid (1.0 g, 7.8 mmol) and sodium bicarbonate (NaHCO3, 1.63 g, 1.4 mmol). 19.4 mmol) in a mixed acetonitrile/water (100 mL, 1:1 v/v) solution. The reaction mixture was stirred overnight at room temperature. Upon completion of the reaction, most of the solvent was removed by distillation under reduced pressure. Subsequently, the pH of the reaction mixture was adjusted to 2 with 2N hydrochloric acid (HCl) and extracted with dichloromethane (DCM). The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate (Na2SO4) and then concentrated. Finally, the residue was purified by silica gel fast column chromatography (petroleum ether/ethyl acetate=20:1) to afford the target product 1 -(((9H-fluoren-9-yl)methoxy)carbonylamino)cyclopentanecarboxylic acid (Compound 4 of Example A, 0.75 g, 28% yield) as a white solid.
