[Synthesis]
3.74 g (20.5 mmol) of L-aspartic acid-β-methyl ester hydrochloride was dissolved in 85 mL of mixed dioxane/H2O (2:1) solvent and 2.21 g (20.8 mmol) of Na2CO3 was added at 0 °C. After the reaction was carried out for 30 min, 2.21 g (20.8 mmol) of Na2CO3 and 5 g (25.7 mmol) di-tert-butyl dicarbonate (Boc2O) and stirred at room temperature overnight. After 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 ether (2 × 25 mL), followed by acidification with 100 mL of 1 M NaHSO4 to pH = 3, and then the aqueous layer was extracted with ether (3 × 75 mL). The organic layers were combined, dried with MgSO4, filtered and the solvent evaporated, and the residue was purified by column chromatography using ethyl acetate as eluent to afford the target product 2-(S)-(tert-butoxycarbonylamino)-(methoxycarbonyl)butanoic acid (Boc-L-aspartic acid 4-methyl ester) 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 (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=8.5Hz, 1H, NHBoc), 10.8 (sl, 1H, COOH).13C NMR (75MHz, 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]
[1] Heterocycles, 1997, vol. 46, # 1, p. 335 - 348
[2] Journal of Organic Chemistry, 1988, vol. 53, # 9, p. 1900 - 1903
[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 |