Z-AIB-OH

Preparation 56 N-[(Benzyloxy)carbonyl1-2-methylalanine To a solution of 2-methylalanine (50 g, 0.49 mmol) and NaA mixture containing sodium carbonate (3 equiv.), 2-amino-2-methylpropanoic acid (1.0 equiv.) and benzyl chloroformate (1.1 equiv.) in water and 1 , 4-dioxane (2:1) was stirred at 23 °C for 24 h. The mixture was diluted in ethyl acetate and washed with IN HC1 solution. The organic layer was dried, filtered and evaporated to deliver the desired intermediate 2-(((benzyloxy)carbonyl)amino)-2-methylpropanoic acid (825 mg, 72percent yield) as a clear oil. 'H NMR (500 MHz, CD3OD) δ ppm 7.32 - 7.38 (m, 5 H), 5.03 - 5.09 (m, 2 H), 1.43 - 1.50 (m, 6 H).Step 1. Synthesis of Compound S.2. To S.1 (10 g, 0.0969 mol) in THF (60 ml) and water (60 mL) at 0° C. was added sodium bicarbonate (16.27 g, 0.193 mole) followed by N-(benzyloxy carbonyloxy) succinimide (60.37 g, 0.242 mol). The reaction mixture was stirred at RT for 12 hr. The THF was removed under vacuum and the aqueous phase was washed with ether (2.x.100 mL). The aqueous phase was cooled to 0° C. and acidified to pH=2 with 5N HCL (50 mL). The reaction mixture was extracted with ethyl acetate (2.x.100 mL); the combined organic layer was dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified by column chromatography (1percent MeOH in dichloromethane) to give S.2 (16 g, 72percent). To S.1 (10 g, 0.0969 mol) in THF (60 ml) and water (60 mL) at 0° C. was added sodium bicarbonate (16.27 g, 0.193 mole) followed by N-(benzyloxy carbonyloxy) succinimide (60.37 g, 0.242 mol). The reaction mixture was stirred at RT for 12 hr. The THF was removed under vacuum and the aqueous phase was washed with ether (2.x.100 mL). The aqueous phase was cooled to 0° C. and acidified to pH=2 with 5N HCL (50 mL). The reaction mixture was extracted with ethyl acetate (2.x.100 mL); the combined organic layer was dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified by column chromatography (1percent MeOH in dichloromethane) to give S.2 (16 g, 72percent). To a stirred solution of 2-amino-2-methylpropanoic acid, HCl (2.0 g, 14.33 mmol) in water (30 ml) at 10°C was added NaAminoisobutyric acid (2.00 g, 19.40 mmol) and sodium carbonate (6.16 g, 58.12 mmol) were dissolved in water (70 cm