Reaction Steps
A stirred solution of 3-amino-3-(3-ethoxy-4-methoxyphenyl)propanoic acid (3.00 g, 12.5 mmol) and 4-methylphthalic anhydride (2.13 g, 12.5 mmol, 95%) in acetic acid was heated to reflux under nitrogen for 18 hours. The mixture was allowed to cool to room temperature. The solvent was removed in vacuo to give an oil. The resulting oil was stirred with ethyl acetate (10 mL), hexane (10 mL) and water (30 mL) for 30 minutes. The resulting suspension was filtered. The solid was washed with water (3×10 mL) and hexane (3×10 mL), and then was dried in a vacuum oven overnight (60 ° C., <1 torr) to give 3-(3-ethoxy-4-methoxyphenyl)-3-(4-methylphthalimido)propanoic acid as a white solid (3.4 g, 71% yield): mp, 134.0–136.0° C.; 1H NMR (DMSO-d6) δ 1.31 (t, J=6.9 Hz, 3H, CH3), 2.47 (s, 3H, CH3), 3.23 (dd, J=6.7, 16.5 Hz, 1H, CHH), 3.50 (dd, J=9.2, 16.5 Hz, 1H, CHH), 3.72 (s, 3H, CH3), 3.97 (q, J=6.9 Hz, 2H, CH2), 5.58 (dd, J=6.7, 9.1 Hz, 1H, NCH), 6.90–6.95 (m, 2H, Ar), 7.01 (br s, 1H, Ar), 7.61–7.76 (m, 3H, Ar), 12.4 (br s, 1H, OH); 13C NMR (DMSO-d6) δ 14.65, 21.32, 36.09, 50.04, 55.45, 63.72, 111.79, 112.15, 119.29, 123.08, 123.58, 128.51, 131.35, 131.49, 134.95, 145.63, 147.75, 148.53, 167.67, 167.78, 171.72; Anal Calcd for C21H21NO6: C, 65.79; H, 5.52; N, 3.65. Found: C, 65.46; H, 5.57; N, 3.31.
