(2S)-4-[[(1,1-Dimethylethoxy)carbonyl]amino]-2-[[(phenylmethoxy)carbonyl]amino]butanoic acid

24424-99-5

62234-40-6

49855-91-6

GENERAL STEPS: Sodium bicarbonate (3.13 g, 37.3 mmol) was added to a mixed solution of (S)-4-amino-2-(((benzyloxy)carbonyl)amino)butanoic acid (4.70 g, 18.6 mmol) in tetrahydrofuran (50 mL) and water (50 mL). The reaction mixture was stirred at room temperature for 5 minutes, followed by slow dropwise addition of a solution of di-tert-butyl dicarbonate (4.88 g, 22.4 mmol) in tetrahydrofuran (50 mL) over 10 minutes. The reaction mixture was continued to be stirred at room temperature for 16 hours. Upon completion of the reaction, most of the tetrahydrofuran was removed by vacuum concentration. The residual aqueous solution was acidified to pH 2 by dropwise addition of aqueous 2 M hydrochloric acid and subsequently extracted with ethyl acetate (100 mL, then 50 mL). The combined organic phases were washed sequentially with water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuum to afford the target product (S)-2-(((benzyloxy)carbonyl)amino)-4-((tert-butoxycarbonyl)amino)butanoic acid as a colorless oil (6.65 g, 98% yield). The product was characterized by 1H NMR (500 MHz, DMSO-d6) and LC/MS (System A): 1H NMR δ 12.60 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.41-7.24 (m, 5H), 6.87-6.76 (m, 1H), 5.03 (s, 2H), 4.00-3.92 (m, 1H), 3.06-2.90 (m, 2H), 1.92-1.77 (m, 1H), 1.71-1.59 (m, 1H), 1.37 (s, 9H); LC/MS m/z (ESI+) = 375 [M + Na+], Rt = 1.06 min, UV purity = 97%.