Synthesis
General procedure for the synthesis of (S)-4-amino-2-((tert-butoxycarbonyl)amino)butanoic acid from BOC-L-glutamine: to a mixed solution of (S)-5-amino-2-(tert-butoxycarbonylamino)-5-oxopentanoic acid (2 g, 8.1 mmol) in DMF and water (1:1, v/v, 18 ml) was added pyridine (1.3 ml, 16.2 mmol). The reaction mixture was stirred at room temperature for 5-10 min. Subsequently, iodobenzene diacetate (3.92 g, 12.1 mmol) was added and the reaction was continued with stirring for 4 hours. After completion of the reaction, deionized water (100 ml) was added to the reaction mixture and extracted with ethyl acetate (3 x 100 ml). The organic phases were combined and washed sequentially with deionized water (100 ml) and saturated saline (100 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by ether milling and after evaporation of the product grades, 1.1 g (62% yield) of the target compound was obtained as a brown solid. LC-MS analysis showed m/z = 219.1 (M + H).
References
[1] Synthetic Communications, 2004, vol. 34, # 6, p. 1049 - 1056
[2] Journal of Medicinal Chemistry, 2009, vol. 52, # 15, p. 4650 - 4656
[3] Bioorganic and Medicinal Chemistry, 1999, vol. 7, # 1, p. 161 - 175
[4] Patent: WO2014/151472, 2014, A1. Location in patent: Paragraph 00340-00341
[5] Patent: WO2016/40315, 2016, A1. Location in patent: Paragraph 00383; 00384
