Reaction Steps
To a stirred solution of cyanomethylphosphonic acid diethyl ester (0.38 mL, 2.4 mmol) in THF (8 mL) in an ice bath was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 2.3 mL, 2.3 mmol) dropwise. The mixture was stirred at room temperature for 40 min. (3-Ethoxy-4-methoxy-phenyl)-(3-fluoro-4-methoxy-phenyl)-methanone (0.35 mg, 1.2 mmol) was added to the mixture. The mixture was refluxed overnight. The solution was poured into ice water (30 ml). The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers was washed with water (50 mL), sodium hydrogen carbonate (50 mL, sat), brine (50 mL) and dried over magnesium sulfate. Removal of solvent and chromatography (Silica Gel) gave a mixture of (E/Z) 3-(3-ethoxy-4-methoxy-phenyl)-3-(3-fluoro-4-methoxy-phenyl)-acrylonitrile as an off-white solid (0.26 g, 69% yield) (isomer ratio is 1:0.8 by HNMR): mp: 122-124° C.; 1H NMR (DMSO-d6) δ 1.31 (t, J=7 Hz, 3H, CH3), 3.78 (s, 3H, CH3), [4.83 and 3.87 (2s)], 3.94 (s, 3H, CH3), 4.01 (q, J=7 Hz, 2H, CH2), [6.15 (s)], 6.21 (s, 1H, CH), 6.74 (dd, J=2, 8 Hz, 1H, Ar), 6.92-7.36 (m, 5H, Ar); 13C NMR (DMSO-d6) δ 14.56, 14.58, 55.49, 56.08, 56.16, 63.84, 93.60, 93.82, 111.39, 111.59, 112.07, 113.53, 113.65, 113.75, 115.34, 115.64, 116.69, 116.99, 118.56, 122.27, 122.33, 125.70, 125.74, 120.22, 126.27, 128.84, 129.59, 129.70, 130.12, 130.86, 130.96, 147.47, 147.89, 148.12, 148.28, 148.88, 149.04, 149.18, 150.27, 151.18, 152.79, 153.06, 159.99, 160.09; Anal. Calcd for C19H18NO3F: C, 69.71; H, 5.54; N, 4.28. Found: C, 69.55; H, 5.58; N, 4.25.
