Fmoc-L-beta-glutamic acid 5-tert-butyl ester

244031-63-8

209252-17-5

The general procedure for the synthesis of (R)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid from the compound (CAS:244031-63-8) was as follows: the (R)-1-(carbonyl)-3-(tert-butoxycarbonyl)propan-2-ylcarbamate [4]aspartic acid (tBu)OH (2.0 g , 4.9 mmol, 1 equiv) was dissolved in anhydrous THF (20 mL). Triethylamine (0.74 mL, 5.4 mmol, 1.1 eq.) and ethyl chloroformate (0.52 mL, 5.4 mmol, 1.1 eq.) were added sequentially at -15 °C. Stirring was continued for 15 minutes and then the solution was allowed to warm to 0°C. Meanwhile, N-methylnitrosourea (2.5 g, 24.3 mmol, 5 eq.) was stirred in ice-cold ether (20 mL) and 40% KOH (20 mL, ice-cold) was added dropwise until completely dissolved. The yellow diazomethane solution in ether was added dropwise to the amino acid solution at 0 °C, then allowed to warm to room temperature and stirred for an additional 2.5 hours. The excess diazomethane was decomposed by dropwise addition of acetic acid. The solution was washed with saturated NaHCO3, saturated NH4Cl and brine. The organic layer was dried with Na2SO4 and evaporated under reduced pressure. The resulting diazomethane was dissolved in water/dioxane (1:5, v/v, 160 mL). After addition of silver benzoate (0.12 g, 0.5 mmol, 0.1 eq.), the mixture was sonicated in an ultrasonic bath until complete conversion (30 min) was monitored by TLC (MeOH/DCM, 1:20, Rf: 0.1-0.2). After evaporation of dioxane under reduced pressure, the solution was acidified with 5% HCl and the precipitate was extracted with EtOAc (three times). The organic layer was dried with Na2SO4 and evaporated under reduced pressure, and the crude product was purified by fast chromatography (MeOH/DCM, 1:20, Rf: 0.1-0.2) to afford [4] (1.3 g, 3.1 mmol, 63% yield).1H NMR (250 MHz, DMSO-d6): δ 12.2 (s, br, 1H), 7.90 (d, 2H), and 7.69 (dd, 2H), 7.42 (t, 2H), 7.33 (m, 3H), 4.27 (m, 3H), 3.59 (m, 1H), 2.41 (m, 4H), 1.38 (s, 9H).13C NMR (75 MHz, DMSO-d6): 172.49, 170.24, 144.35, 141.19 128.07, 127.51, 125.63, 120.56, 80.39, 65.80, 60.20, 47.17, 44.81, 28.13. Rt (10-100%): 23.5 min. ESI (m + Na): 448.1.