D-Aspartic acid, N-[(1,1-dimethylethoxy)carbonyl]-, 4-methyl ester

Synthesis

3.74 g (20.5 mmol) of L-aspartic acid-β-methyl ester hydrochloride was dissolved in 85 mL of dioxane/H2O (2:1) mixed solvent at 0 °C, to which 2.21 g (20.8 mmol) of Na2CO3 was added. 30 min later, another 2.21 g (20.8 mmol) of Na2CO3 and 5 g ( 25.7 mmol) di-tert-butyl dicarbonate (Boc2O), followed by stirring the reaction at room temperature overnight. Upon completion of the reaction, the solvent was removed by vacuum concentration and the residue was poured into 60 mL of ice water. The aqueous layer was washed with 2 x 25 mL of ether and then acidified with 100 mL of 1 M NaHSO4 to pH=3, after which the aqueous layer was extracted with ether (3 x 75 mL). The organic layers were combined and dried with MgSO4. After filtration and evaporation of the solvent, the residue was purified by column chromatography using ethyl acetate as eluent to afford the target product 2-(S)-(tert-butoxycarbonylamino)-(methoxycarbonyl)butanoic acid in 75% yield. The product was a white solid with an Rf value of 0.50 (ethyl acetate) and [α]D=+28.6 (c=0.3; CHCl3).IR Spectrum (cm-1): 3429 (NH), 2979 (CH), 1714 (C=O), 1509,1438,1394,1367,1156,1057,1026,843,780. 734.1H NMR (300 MHz, CDCl3): δ (ppm) = 1.42 (s, 9H, CH3), 2.82 (dd, J=4.8,17.2 Hz, 1H, CH2), 3.02 (dd, J=17.2,4.1 Hz, 1H, CH2), 3.69 (s, 3H, OCH3), 4.59-4.62 ( m, 1H, CHN), 5.57 (d, J=8.5 Hz, 1H, NHBoc), 10.8 (sl, 1H, COOH).13C NMR (75 MHz, CDCl3): δ (ppm) = 28.2 (CH3), 36.4 (CH2), 49.7 (CHN), 52.1 (OCH3), 80.5 (C(CH3 )3), 155.6 (COO), 171.6 (COO), 175.8 (COO). Elemental analysis (C10H17NO6) Calculated values: C 48.58, H 6.93, N 5.67; measured values: C 48.64, H 7.04, N 5.68.

References

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[3] Chemical Communications, 2001, # 18, p. 1710 - 1711
[4] Patent: WO2013/30193, 2013, A1. Location in patent: Page/Page column 30; 31
[5] RSC Advances, 2015, vol. 5, # 88, p. 71868 - 71872