Reaction Steps
To a stirred solution of 3-(3',4'-dimethoxyphenyl)-3-(1'-oxoisoindolinyl)-1-propanol (500 mg, 1.53 mmol), ethyl bromide (0.27 mL, 3.62 mmol) and tetrabutyl ammonium iodide (60 mg, 0.16 mmol) in THF (10 mL) at room temperature, was added NaH (160 mg, 60%, 4.0 mmol). The mixture was stirred at room temperature for 4 h. To the mixture was added NH4Cl (20 mL, sat). The organic layer was separated. The aqueous layer was extracted with methylene chloride (2×25 mL). The combined organic layer was dried over magnesium sulfate. Removal of solvent and chromatography (silica gel 120 grams, 1:6 EtOAc:CH2Cl2) gave 3-(3',4'-dimethoxyphenyl)-1-ethoxy-3-(1'-oxoisoindolinyl)propane as an oil, (420 mg, 77% yield): 1H NMR (CDCl3)δ1.09 (t, J=7 Hz, 3H, CH3), 2.35-2.45 (m, 2H, CH2), 3.35-3.58 (m, 4H, CH2 OCH2), 3.84 (s, 3H, CH3), 3.86 (s, 3H, CH3), 4.00 (d, J=16.8 Hz, 1H, NCHH), 4.35 (d, d=16.8 Hz, 1H, NCHH), 5.66 (dd, J=6, 9.3 Hz, 1H, NCH), 6.82-6.98 (m, 3H, Ar), 7.35-7.53 (m, 3H, Ar), 7.84-7.88 (m, 1H, Ar); 13C NMR (CDCl3)δ15.02, 31.62, 45.82, 51.51, 55.82, 55.90, 66.39, 67.86, 110.90, 111.27, 119.15, 122.68, 123.71, 127.86, 131.16, 132.28, 132.73, 141.28, 148.49, 149.08, 168.38; Anal Calcd for C21H25NO4 0.3H2O: C, 69.90; H, 7.15; N, 3.88. Found: C, 69.69; H, 6.80; N, 3.73.
