2-[1-[(2-methylpropan-2-yl)oxycarbonyl]-3-oxopiperazin-2-yl]acetic acid

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Carboxymethyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (1.87 g, 7.25 mmol), 3-chloro-N-hydroxy-benzamidine (1.36 g, 7.98 mmol), HOBt (1.08 g, 7.98 mmol) and EDCl (1.53 g, 7.98 mmol) in DMF (20 mL) were stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water (3 times), saturated sodium bicarbonate (2 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was dissolved in DMF (20 mL) and then heated at 135° C. for 4 hours. After cooling, the reaction mixture was diluted with ethyl acetate, washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification was performed by flash chromatography on silica gel using hexanes:dichloromethane (1:1) to afford the titled compound (1.48 g, 52%, white foam solid). 1H NMR (CDCl3) δ (ppm): 8.08 (m, 1H), 7.97 (m, 1H), 7.46 (m, 2H), 6.35 (m, 1H), 5.04 (m, 1H), 4.31 (m, 1H), 3.68 (m,1H), 3.50 ( m, 2H), 3.27 (m, 2H), 1.35 (bs, 9H). washed with water (3 times), saturated sodium bicarbonate (2 times) and brine dried over anhydrous sodium sulfate filtered concentrated The residue was dissolved in DMF (20 mL) After cooling the reaction mixture was diluted with ethyl acetate washed with water (3 times) and brine dried over anhydrous sodium sulfate filtered concentrated Purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1N Sodium hydroxide (11.4 mL, 11.4 mmol) was added to 2-ethoxycarbonylmethyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (2.5 g, 8.73 mmol) in methanol (20 mL) at room temperature and then stirred for 2.5 hours. The reaction mixture was concentrated, acidified with 2N HCl to pH˜2 and extracted with dichloromethane (3 times). The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford the titled compound (1.87 g, 83%, white foam solid). 1H NMR (CDCl3) δ (ppm): 7.68 (bs, 1H), 4.78 (m, 1H), 4.19 (m, 1H), 3.45 (m, 1H), 3.34 (m, 2H), 2.97 (m, 2H), 1.49 (s, 9H). The reaction mixture was concentrated extracted with dichloromethane (3 times) The organic layer was washed with brine dried over anhydrous sodium sulfate filtered concentrated