[Synthesis]
To a 250 mL round bottom flask was added 50.0 g (0.42 mol) of p-toluylaldehyde, 47.6 g (0.46 mol) of malonic acid and 64.2 g (0.83 mol) of ammonium acetate dissolved in ethanol. The reaction mixture was heated to 80-90°C under stirring and refluxed for 7.5 hours. Upon completion of the reaction, the mixture was cooled to 0-5°C and stirred for 30 min, followed by filtration to afford 51.4 g of 3-amino-3-(p-tolyl)propionic acid (racemic mixture) as a white powder (68.9% isolated yield based on p-toluylaldehyde).
The physical properties of 3-amino-3-(p-tolyl)propionic acid (racemic mixture) are as follows:
1H-NMR (δ, ppm, D2O + DCl): 2.30 (s, 3H), 3.04 (dd, 1H, J = 17.1, 6.8 Hz), 3.20 (dd, 1H, J = 17.1, 7.3 Hz), 4.74 (dd, 1H, J = 7.3, 6.8 Hz), 7.29 (d, 2H, J = 8.3 Hz), 7.36 (d, 2H, J = 8.3 Hz).
13C-NMR (δ, ppm, D2O + DCl): 23.4, 40.7, 54.4, 130.0, 133.0, 135.0, 143.1, 176.3.
MS (EI) m/z: 179 (M+).
MS (CI, i-C4H10) m/z: 180 (MH+).
Elemental analysis: Calculated C, 67.02%; H, 7.31%; N, 7.82%. Measured values C, 67.05%; H, 7.40%; N, 7.66%. |
[References]
[1] Patent: EP1621529, 2006, A1. Location in patent: Page/Page column 27-28
[2] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 252 - 268
[3] Advanced Synthesis and Catalysis, 2010, vol. 352, # 2-3, p. 395 - 406
[4] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 11, p. 1207 - 1212
[5] Bulletin de la Societe Chimique de France, 1987, # 6, p. 1079 - 1083 |