3-Methoxy-4-[(4-methoxybenzyl)oxy]benzaldehyde (20.0 g, 73.4 mmol) and 3-morpholinopropronitrile (Lancaster, 11.0 g, 77.1 mmol) were stirred in DMSO (15 mL) at 65 C until the mixture was homogeneous. The solution was cooled to 40 C and sodium methoxide (0.79 g, 14.7 mmol) was added. The mixture was stirred at 75 C for 15 minutes, then cooled to room temperature and diluted with dichloromethane (150 mL) and water (200 mL). 1N HCl (25 mL) was added and the two layers were seperated. The organics were combined and dried (magnesium sulfate), filtered and concentrated to a red oil (29.5 g, 73 mmol) that was used directly in the synthesis of 3-anilino-2-{3-methoxy-4-[(4-methoxybenzyl)oxy]benzyl}prop-2-enenitrile. 1H NMR (300 MHz, d6-DMSO): δ 7.38 (d, 2H), 7.03-6.95 (m,3H), 6.84 (t, J=13.5 Hz, 2H), 6.73 (d, J=8.2 Hz, 1H), 4.98 (s, 3H), 3.78 (s, 3H), 3.76 (s, 3H), 3.66-3.60 (m, 2H), 3.55-3.50 (m, 3H), 3.46-3.43 (m, 2H), 3.36 (s, 1H), 3.33-3.29 (m, 2H). MS (ES+, m/z)=395 (M+H).
