Z-ASP-OME

67-56-1

4515-23-5

4668-42-2

The general procedure for the synthesis of (S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutanoic acid from methanol and Z-aspartic anhydride was as follows: 49.0 g (196 mmol) of benzyl (S)-(2,5-dioxo-tetrahydrofuran-3-yl)carbamate obtained from Steps 1-1 (2) was dissolved in 100 mL of ethyl acetate, followed by adding 150 mL of methanol and the reaction was stirred at room temperature for 5 hours. Upon completion of the reaction, the mixture was concentrated to dryness under reduced pressure and the resulting residue was dissolved in 200 mL of diisopropyl ether. 34 mL of dicyclohexylamine was added slowly and dropwise with stirring to produce (S)-3-((benzyloxycarbonyl)amino)-4-methoxy-4-oxobutanoic acid dicyclohexylamine salt. The salt was collected by filtration and suspended in 200 mL of distilled water. 200 mL of ethyl acetate was added and the pH was adjusted with 6N hydrochloric acid to 2. After phase separation was carried out, the organic layer was washed several times with distilled water, dried with anhydrous magnesium sulfate and subsequently concentrated under reduced pressure. To the concentrated residue 200 mL of diethyl ether and 20 mL of petroleum ether were added to promote crystallization. The resulting crystals were filtered to give 32.3 g of (S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutanoic acid in 54% yield. The product was characterized by 1H NMR (300 MHz, CDCl3): δ 7.37 (m, 5H), 5.76 (d, 1H), 5.13 (s, 1H), 4.65 (m, 1H), 3.76 (s, 2H), 3.00 (dd, 2H).