Reaction Steps
A mixture of 3-amino-3-(3'-ethoxy-4'-methoxyphenyl)-1-propanol (8.4 grams, 37.3 mmol) and sodium carbonate (3.95 grams, 37.3 mmol) in acetonitrile and water (40 mL each) was stirred at room temperature for 15 minutes. To the solution was added N-carbethoxyphthalimide (8.18 grams, 37.3 mmol) as solid. After 20 minutes, the acetonitrile was removed under vacuum. The aqueous solution was extracted with methylene chloride (3×50 mL). The combined organic layers were washed with HCl (40 mL, 1N), and dried over magnesium sulfate. Removal of solvent gave a green oil. Ether (25 mL) was added to the oil, then hexane (2 mL) was added. A suspension formed and the solid was filtered to give 3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimido-1-propanol as a white solid, 1 g. The mother liquor was purified by chromatography (silica gel 500 grams, 10, 15, 20% EtOAc/CH2Cl2) to give 3-(3'-ethoxy-4'-methoxyphenyl)-3-phthalimido-1-propanol as a solid, 2.54 g. Total yield was 3.54 g (27% yield): mp, 112.0°-114.0° C.; 1H NMR (CDCl3)δ1.45 (t, J=7 Hz, 3H, CH3), 1.59-1.65 (br s, 1H, OH), 2.49-2.59 (m, 1H, CHH), 2.71-2.83 (m, 1H, CHH), 3.66-3.69 (m, 2H, OCH2), 3.84 (s, 3H, CH3), 4.10 (q, J=7 Hz, 2H, MeCH2), 5.53 (dd, J=6.5, 9.5 Hz, 1H, NCH), 6.81 (d, J=8.2 Hz, 1H, Ar), 7.09-7.27 (m, 2H, Ar), 7.66-7.72 (m, 2H, Ar), 7.76-7.82 (m, 2H, Ar); 13C NMR (CDCl3)δ14.72, 33.86, 51.46, 55.88, 59.84, 64.34, 111.16, 113.05, 120.68, 123.20, 131.64, 131.86, 133.94, 148.17, 148.97, 168.49; Anal Calcd for C20H21NO5 : C, 67.59; H, 5.96; N, 3.94. Found: C, 65.40; H, 5.81; N, 3.84.
