The general procedure for the synthesis of (S)-2-((tert-butoxycarbonyl)amino)-3-(3-fluorophenyl)propionic acid from di-tert-butyl dicarbonate and L-3-fluorophenylalanine was as follows: first, L-2-amino-3-(3-fluorophenyl)-propionic acid (20.0 g, 110 mmol, 1 eq.) was dissolved in water (100 mL) and sodium carbonate (16.2 g. 153 mmol, 1.4 eq.) in water (40 mL). Subsequently, 1,4-dioxane (100 mL) was added and the mixture was cooled to 0 °C. Di-tert-butyl dicarbonate was added with stirring and the reaction mixture was then stirred at room temperature for 5 hours. After the reaction was complete, the dioxane was removed by evaporation. Water (125 mL) was added to dilute the reaction mixture, which was subsequently washed with ether (2 x 100 mL). The aqueous phase was acidified with 10% citric acid and then extracted with ethyl acetate (2 x 300 mL). The organic phases were combined, washed sequentially with water (2×150 mL) and brine (150 mL), dried with anhydrous sodium sulfate, and concentrated to afford the target product (S)-2-((tert-butoxycarbonyl)amino)-3-(3-fluorophenyl)propionic acid as a colorless viscous oil, which slowly solidified after standing (31 g, quantitative yield). The 1H NMR (CDCl3) data of the product were as follows: δ 7.33-7.26 (m, 1H), 7.00-6.91 (m, 3H), 4.96 (s, 1H), 4.62 (bs, 1H), 3.23 (dd, J = 14, 5.3Hz, 2H), 1.44 (s, 9H). Elemental analysis (C14H18NO4F) calculated values: C, 59.36; H, 6.40; N, 4.94. measured values: C, 59.29; H, 6.34; N, 4.90.
