(S)-4-Amino-5-tert-butoxy-5-oxovaleric acid (1.50 g, 7.38 mmol) was dissolved in 1,4-dioxane (40 mL) and cooled to 0 °C. An aqueous solution of sodium carbonate (196 mg, 1.85 mmol) (20 mL) and Fmoc-Cl (2.11 g, 8.16 mmol) were added sequentially. The reaction mixture was slowly warmed to room temperature and stirred for 16 hours. Upon completion of the reaction, the pH was adjusted to slightly acidic (pH ≈ 6) with 2 M hydrochloric acid, and the pH was adjusted with 1 M citric acid (ca. 80 mL) to ca. 3. The reaction mixture was extracted with ethyl acetate (3 x 100 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent being a 3:2 solvent mixture of ethyl acetate/hexane to afford (S)-4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid (3.10 g, 99%) as a white solid.1H NMR (300 MHz, CDCl3) δ: Carboxylic acid peak (1H) not observed (due to broad signal), 7.76 (d, J = 7.5 Hz, 2H), 7.61-7.58 (m, 2H), 7.42-7.26 (m, 4H), 5.45 (d, J = 7.8 Hz, 1H), 4.48-4.19 (m, 4H), 2.51-2.34 (m, 2H), 2.28-2.14 (m, 1H), 1.99 -1.88 (m, 1H), 1.47 (s, 9H); ESI MS m/z = 448 [M + Na]+.
