A solution of 4-{(glycylamino}methyl)-1-(tert-butoxycarbonyl)piperidine (1.33 g, 4.90 mmol) in CH2Cl2 (25 mL) was treated with Et3N (0.75 mL, 5.4 mmol), 2-amino-5-chlorobenzoic acid (840 mg, 4.9 mmol), EDCI (940 mg, 4.9 mmol) and HOBt (660 mg, 4.9 mmol). After the reaction mixture was stirred at room temperature for 3 h, 2 N aqueous NaOH solution (20 mL) was added. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (20 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, ethyl acetate) afforded the desired 4-[{(N-(2-amino-5-chlorobenzoyl)glycyl)amino}methyl]-1-(tert-butoxycarbonyl)piperidine (1.63 g, 78%) as a solid.
