Synthesis
General procedure: A mixture of iminodiacetic acid (5.1 g, 38.3 mmol) and sodium bicarbonate (NaHCO3, 12.9 g, 153 mmol) was dissolved in 50 mL of water. After the gas release stopped, 50 mL of tetrahydrofuran (THF) was added, followed by the slow addition of di-tert-butyl dicarbonate (Boc2O, 10.0 g, 46.0 mmol). The reaction mixture was stirred at room temperature for 2 days and the progress of the reaction was monitored by electrospray ionization mass spectrometry (ESI-MS) until complete consumption of the feedstock. Upon completion of the reaction, THF was removed by rotary evaporation and the aqueous phase was washed twice with ether (Et2O). Subsequently, the pH of the aqueous phase was adjusted with concentrated hydrochloric acid to 1. The product was extracted with ethyl acetate (EtOAc), and after combining the organic phases, the solvent was removed by rotary evaporation to give a white solid product. The product was further purified by recrystallization from ethyl acetate to give N-Boc-iminodiacetic acid (8.04 g, 90% yield) as clear crystals.ESI-MS detection showed [M-H]- peak at m/z 232.1.
References
[1] Journal of Medicinal Chemistry, 1996, vol. 39, # 8, p. 1601 - 1608
[2] Patent: WO2004/35576, 2004, A2. Location in patent: Page 170
[3] Patent: WO2005/117904, 2005, A2. Location in patent: Page/Page column 404-405
[4] Tetrahedron, 1996, vol. 52, # 29, p. 9793 - 9804
[5] Bioorganic and Medicinal Chemistry, 1998, vol. 6, # 8, p. 1347 - 1378
