Reaction Steps
To a stirred suspension of 3-(3',4'-dimethoxyphenyl)-3-(1'-oxoisoindolinyl)propionic acid (3.74 grams, 10.96 mmol) in THF (60 mL) at -10°-15° C. (ice-salt bath), was added borane in THF (11 mL, 1M, 11 mmol). The suspension was allowed to warm to room temperature slowly overnight. To the resulting clear solution was added water (20 mL), followed by potassium carbonate (6 g). The organic layer was separated. The aqueous layer was extracted with methylene chloride (2×50 mL). The combined organic layers were washed with sodium carbonate (20 mL, sat), brine (20 mL), and dried over magnesium sulfate. Removal of solvent and chromatography (silica gel, 100 grams, 1:2, 1:1 EtOAc/CH2Cl2) gave 3-(3',4'-dimethoxyphenyl)-3-(1'-oxoisoindolinyl)-1-propanol as an oil, (2.52 grams, 70%). Ether (6 mL) and 2 drops of methanol were added to the oil. Hexane was added until the solution was turned cloudy. The mixture was stirred for 30 minutes to give a white solid and the solid was filtered: mp, 101.5°-103.0° C.; 1H NMR (CDCl3)δ1.99-2.36 (m, 3H, CH2, OH), 3.49-3.80 (m, 2H, OCH2), 3.85 (s, 3H, CH3), 3.89 (s, 3H, CH3), 3.91 (d, J=17.2 Hz, 1H, CHH), 4.19 (d, J=17.2 Hz, 1H, CHH), 5.75 (dd, J=4, 11.5 Hz, 1H, NCH), 6.86-7.00(m, 3H, Ar), 7.27-7.56 (m, 3H, Ar), 7.86-7.89 (m, 1H, Ar); 13C NMR (CDCl3)δ33.87, 46.22, 50.61, 55.91, 56.01, 58.55, 111.04, 111.73, 119.66, 122.81, 123.89, 128.64, 131.33, 131.56, 132.09, 141.35, 148.81, 148.24, 169.45; Anal Calcd for C19H21 NO4 : C, 69.71; H, 6.47; N, 4.28. Found: C, 69.5I; H, 6.27; N, 4.12.
