To a solution of tert-butyl piperazine-1-carboxylate (2.0 g, 10.74 mmol) in THF (20 mL) was added Et3N (2.17 g, 21.48 mmol) and tert-butyl bromoacetate (2.09 g, 10.74 mmol). The resulting mixture was stirred at room temperature for 12 hours and then partitioned between ethyl acetate (200 mL) and water (100 mL). The organic layer was separated and washed with brine (100 mL), then dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (eluent: PE/EA = 5/1, v:v) to afford tert-butyl 4-(2-tert-butoxy-2-oxo-ethyl)piperazine-1-carboxylate (2.5 g) as a white solid. A mixture of tert-butyl 4-(2-tert-butoxy-2-oxo-ethyl)piperazine-1-carboxylate (1.0 g, 3.3 mmol) and MeOH solution of HCl (1.0 M, 15 mL) was stirred at room temperature for 12 hours. The formed mixture was concentrated in vacuum. The residue was dissolved in MeOH (10 mL) and then treated with alkali resin and filtered. The filtrate was concentrated in vacuum to give 2-(piperazin-1-yl)acetic acid hydrate (350 mg) as a white solid.
