Synthesis
3,4-dimethoxybenzaldehyde (50 g, 0.33 mol) and ammonium acetate (50 g) were mixed in 95% ethanol (50 ml). The mixture was heated to 50 °C, followed by slow addition of malonic acid (63 g, 0.6 mol) and supplemented with 95% ethanol (25 ml). The reaction mixture was refluxed for 3 hours and then the reaction was continued at 80°C for 24 hours. Upon completion of the reaction, the precipitate was collected by filtration, washed with ethanol and recrystallized in 50% ethanol to afford 47.8 g of the target product 3-amino-3-(3,4-dimethoxyphenyl)propionic acid as a white solid (yield: 65%). The product was characterized by 1H NMR (300 MHz, D2O): δ 6.90-6.87 (m, 3H), 4.44-4.39 (t, 1H), 3.69 (s, 3H), 3.67 (s, 3H), 2.76-2.57 (m, 2H). Mass spectrum (EI) m/z: 226 (M++H).
References
[1] Chemical Communications, 2011, vol. 47, # 20, p. 5894 - 5896
[2] Patent: WO2010/16939, 2010, A1. Location in patent: Page/Page column 57
[3] Synlett, 2013, vol. 24, # 6, p. 733 - 736
[4] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 11, p. 1207 - 1212
[5] Tetrahedron Asymmetry, 2008, vol. 19, # 17, p. 2072 - 2077
