29248-48-4

6066-82-6

31972-52-8

29248-48-4

GENERAL STEPS: Boc-glycylglycine (1.00 g, 7.57 mmol) was dissolved in a solvent mixture of dioxane and water (30:5 mL) at room temperature, and triethylamine (1.15 g, 11.4 mmol) and di-tert-butyl dicarbonate (1.84 g, 8.33 mmol) were added sequentially. The reaction mixture was stirred overnight at room temperature, then diluted with water, the pH was adjusted to about 2 by addition of solid KHSO4, extracted with EtOAc, and the organic phase was dried with anhydrous Na2SO4 and concentrated under reduced pressure to give (tert-butoxycarbonyl)glycylglycine [8] as a white solid. The crude (tert-butoxycarbonyl)glycylglycine (0.106 g, 0.451 mmol) was dissolved in anhydrous dichloromethane (5.00 mL) and triethylamine (45.6 mg, 0.451 mmol) and propylphosphinic anhydride (T3P) [9] (0.344 g, 0.541 mmol) solution was added. The mixture was stirred at room temperature for 20 min before N-hydroxysuccinimide (51.9 mg, 0.451 mmol) was added. The reaction was continued to stir for 48 h. Upon completion, the organic layer was washed with brine (3 times), dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product as a white solid. The crude product was purified by ether milling to afford 65.4 mg (44% yield) of the target compound 2,5-dioxopyrrolidin-1-yl 2-(2-((tert-butoxycarbonyl)amino)acetylamino)acetate as a white solid: 1H NMR (400 MHz, CDCl3) δ 6.76 (brs, 1H), 5.15 (brs, 1H), 4.43 (d , 2H, J = 5.7 Hz), 3.87 (d, 2H, J = 5.3 Hz), 2.85 (s, 4H), 1.45 (s, 9H); ESI-MS m/z 330 [M+H]+. The elemental composition of the products was confirmed to be within 5 ppm error by high-resolution accurate mass measurements (Exactive Plus, Thermo Fisher Scientific) in negative ion mode by direct injection into ESI-MS (see Fig. 1).