Synthesis
Example 1: Synthesis of N-(Boc)-L-glutamine (1): L-glutamine (25 g, 0.17 mol) was dissolved in 300 mL of aqueous NaOH solution (21.9 g, 0.547 mol). The resulting solution was cooled to below 10 °C, followed by the slow addition of a THF (150 mL) solution of Boc anhydride (0.205 mol) (note that the reaction is exothermic). The reaction mixture was stirred continuously at 25 °C for 20 hours. The progress of the reaction was monitored by TLC and the unfolding agent was MeOH:CH2Cl2 (1:1, containing 0.1% AcOH). Upon completion of the reaction, the organic phase was separated and the aqueous phase was extracted with hexane (100 mL) and acidified to pH 2 with 2N HCl, followed by extraction with ethyl acetate (2 x 250 mL). The organic phases were combined, dried with Na2SO4 and the solvent was evaporated in vacuum. The resulting viscous oily product was diluted with dichloromethane and evaporated again. After standing for 2-3 days, it was crystallized from hexane to give N-(Boc)-L-glutamine (1) (37.5 g, 89% yield) as a colorless solid. The product was characterized by 1H NMR (DMSO, 300 MHz) and ESI-MS (m/z: 269 [M+Na]+).
References
[1] Journal of the American Chemical Society, 1997, vol. 119, # 17, p. 4086 - 4087
[2] Patent: WO2015/189856, 2015, A1. Location in patent: Page/Page column 14
[3] Synthetic Communications, 2008, vol. 38, # 2, p. 162 - 169
[4] Bulletin of the Korean Chemical Society, 2012, vol. 33, # 8, p. 2777 - 2780
[5] Organic Syntheses, 1985, vol. 63, p. 160 - 160
