Malonic Acid → 3-Amino-3-(3-ethoxy-4-methoxyphenyl)propanoic acid

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 3-ethoxy-4-methoxybenzaldehyde (119.5 grams, 664 mmol) and ammonium acetate (148.3 grams, 1.92 mol) in ethanol (300 mL, 95%) was heated at 45° C. To the mixture was added malonic acid (69 grams, 664 mmol), followed by ethanol (100 mL, 95%). The mixture was refluxed for 18 hours. The mixture was cooled to room temperature and was stirred for 2 hours. The suspension was filtered and the solid was washed with cold ethanol (5×50 mL) to give 3-amino-3-(3'-ethoxy-4'-methoxyphenyl)propionic acid as a white solid, which was dried in a vacuum oven overnight, (94.75 grams, 60% yield): mp, 224.0°-225.5° C.; 1H NMR (D2O/NaOD)δ1.41 (t, J=7 Hz, 3H, CH3), 2.52-2.56 (m, 2H, CH2), 3.83 (s, 3H, CH2), 4.14 (q, J=7 Hz, 2H, CH2), 4.19 (t, J=7 Hz, 1H, NCH), 6.98-7.04 (m, 3H, Ar); 13C NMR (D2O/NaOD)δ16.75, 49.81, 55.45, 58.46, 67.63, 114.17, 114.71, 121.76, 140.69, 149.91, 150.09, 182.97; Anal. Calcd for C12H17NO4 : C, 60.24; H, 7.16; N, 5.85. Found: C, 60.21; H, 7.12;N, 5.88.

Provenance & Evidence