BOC-D-ASP(OBZL)-OH

White to off-white powder

2-tert-Butoxycarbonylamino-4-hydroxy-butyric acid benzyl ester (1). To a solution of D-Boc-Asp-OBzl (2 g, 6.18 mmol) and NMM (0.62 g, 6.18 mmol) in anhydrous DME (10 mL) at -15 C. was added i-BuO2CCl (0.84 g, 6.18 mmol) slowly. After ten minutes, the precipitated N-methyl morpholine hydrochloride was filtered off, and washed with DME. The filtrate was combined with the washings in a large flask. A solution of sodium borohydride (0.35 g, 9.27 mmol) in water (5 mL) was added right away, producing a strong evolution of gas, followed by water immediately afterwards. The solution was extracted with ethyl acetate. The organic layers were combined and dried over Na2SO4. The combined organic layers were evaporated to dryness below 30 C. and then the crude product (1.65 g, 86 %) was obtained and used directly in the next step. 1H NMR (400 MHz, CDCl3) delta1.43 (s, 9 H), 1.63 (m, 1 H), 2.15 (m, 1H), 3.62-3.69 (m, 2 H), 4.53 (m, 1 H), 5.18 (m, 2 H), 5.41 (d, 1 H), 7.35 (m, 5 H).The first intermediate is obtained by reduction. The specific steps are as follows.In a 250mL three-necked flask, Add 100mL of tetrahydrofuran, Weigh Compound I-a (10g, 1.0eq) was added to the reaction flask, Cooling to 5 ~ 10 , the system was clear state, stirring, Ethyl chloroformate (3.4 g, 1.05 eq) and triethylamine (3.18 g, 1.05 eq) were added slowly, System pH between 8-9, at 5 ~ 10 for 2 ~ 3h.NaBH4 (2.26 g, 2.0 eq) was added slowly, Continue reaction 6 ~ 8h, TLC monitoring until the reaction is complete, add purified water 300mL, Tetrahydrofuran was concentrated, and the residue was extracted with 100 mL × 4 of ethyl acetate.The aqueous phase was adjusted to pH 2-3 with 6N hydrochloric acid, And extracted with methyl tert-butyl ether 200mL × 3, the organic phases were combined, dried, filtered, concentrated, Crystallization with petroleum ether gave compound II-a (5.8 g, yield 61.0%).A mixture of

Boc-D-Asp-OBzl is an aspartic acid derivative[1].