Synthesis
Acetic anhydride (7.50 mL, 80.00 mmol) and concentrated sulfuric acid were added to glacial acetic acid (120 mL) as (S)-5-amino-2-(((benzyloxy)carbonyl)amino)-5-oxopentanoic acid (11.20 g, 40.00 mmol) and triphenylmethanol (20.80 g, 80.00 mmol). The mixture was stirred in an ice bath and then gradually warmed up to 50 °C for 2 hours of reaction. Upon completion of the reaction, the reaction mixture was slowly poured into ice (800 g) and a white precipitate precipitated. The precipitate was collected by filtration and redissolved in ethyl acetate (600 mL). The resulting solution was washed sequentially with water (3 x 200 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Finally, the white solid N-Cbz-N'-trityl-L-glutamine (14.70 g, 70% yield) was obtained by solvent crystallization from ethyl acetate/petroleum ether mixture.
References
[1] Journal of the American Chemical Society, 2013, vol. 135, # 35, p. 12998 - 13007
[2] Journal of Peptide Science, 2010, vol. 16, # 7, p. 364 - 374
[3] Journal of Medicinal Chemistry, 1998, vol. 41, # 15, p. 2786 - 2805
[4] Synthetic Communications, 2017, vol. 47, # 12, p. 1136 - 1141
[5] Tetrahedron Letters, 1991, vol. 32, # 6, p. 739 - 742
