Reaction Steps
A suspension of potassium (0.308 g, 7.87 mmol) in xylenes (6 mL) was heated to 100° C. and stirred rapidly as it was allowed to cool. The xylenes were removed and the potassium was washed with Et2O (×3) and covered with Et2O (10 mL). The mixture was treated with absolute EtOH (1.30 mL, 22.2 mmol) and stirred at reflux until the potassium had dissolved (3 h). The cooled mixture was treated with diethyl oxalate (1.07 mL, 7.87 mmol) then with a solution of the above nitrotoluene (2.00 g, 7.87 mmol) in dry Et2O (5 mL). After 115 h, the dark red precipitate was removed by filtration and washed with Et2O. The red solid (1.189 g) was dissolved in absolute EtOH (45 mL), acidified with AcOH (0.78 mL), and hydrogenated over Pd/C (10%, 0.44 g) at 1 atm H2 for 8 h. The mixture was filtered through Celite, concentrated, diluted with 0.2 M aqueous Na2CO3 (100 mL), and extracted with EtOAc (×4). The combined extracts were washed with water (×2), dried (Na2SO4), evaporated and purified by flash chromatography (2% Et3N/EtOAc) to give ethyl 7-[2-(dimethylamino)-ethoxy]-5-methoxyindole-2-carboxylate as a clear oil (0.44 g, 18%). 1H NMR (CDCl3) δ 10.93 (br s, 1 H, NH), 7.09 (d, J=2.1 Hz, 1 H, H-3), 6.67 (d, J=2.0 Hz, 1 H, H-4), 6.43 (d, J=2.0 Hz, 1 H, H-6), 4.38 (q, J=7.0 Hz, 2 H, OCH2CH3), 4.16 (t, J=6.5 Hz, 2 H, OCH2CH2N), 3.88 (s, 3 H, OCH3), 2.79 (t, J=7.0 Hz, 2 H, NCH2), 2.37 (s, 6 H, N(CH3)2), 1.40 (t, J=6.5 Hz, 3 H, OCH2CH3); 13C NMR δ 161.9 (CO2), 155.0, 146.0, 128.1, 127.7, 124.9 (C-2, 3a, 5, 7, 7a), 108.1 (C-3), 99.1 (C-4), 94.6 (C-6), 65.9 (OCH2CH2N), 60.6 (OCH2CH3), 58.3 (NCH2), 55.6 (OCH3), 45.1 (N(CH3)2), 14.4 (OCH2CH3). Calc for C16H22N2O4, M+306.1580. Found, 306.1577. Starting material (0.77 g, 39%) was recovered from the ethereal washes by extraction into acid, basification, and extraction with Et2O.
