D-Aspartic acid, N-[(1,1-diMethylethoxy)carbonyl]-, 4-(1,1-diMethylethyl) ester

Synthesis

GENERAL METHOD: D-aspartic acid-4-tert-butyl ester (1.89 g, 10 mmol) was dissolved in a solvent mixture of tetrahydrofuran (20 mL) and water (12 mL) at 0 °C. After stirring for 5 minutes, di-tert-butyl dicarbonate (4.35 g, 20 mmol) was added slowly in portions, followed by sodium carbonate (4.20 g, 40 mmol). The reaction mixture was stirred at room temperature for 24 h. After completion of the reaction, the solvent was removed by concentration under reduced pressure. The residue was dissolved in 10% aqueous sodium bicarbonate solution (50 mL) and the aqueous phase was washed with ether (3 x 20 mL). After adjusting the pH of the aqueous phase to 4.0 with citric acid, the product was extracted with ethyl acetate (3 x 100 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford the target product Boc-O-tert-butyl-D-aspartic acid (4-tert-butoxy-2-(tert-butoxycarbonylamino)-4-oxobutanoic acid) as a colorless oil (2.82 g, 97% yield).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 15, p. 4975 - 4978
[2] Patent: WO2017/24009, 2017, A1. Location in patent: Paragraph 0637