Reaction Steps
(Z)-2-(4-(4-Chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethyl pivalate (1 g, 2.16 mmol) was dissolved in THF (8 ml) followed by addition of MeOH (1 ml) and water (1 ml). Sodium hydroxide (0.1 g, 2.5 mmol) was added in one portion and the reaction was stirred at room temperature for 12 h. After completion of the reaction the mixture was partitioned between water (20 ml) and EtOAc (20 ml). Organic phase was washed with water (20 ml) and brine (20 ml), dried (Na2SO4), filtered and concentrated. The residue was crystallized from i-PrOH yielding ospemifene (0.29 g, 35%) as a white solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 7.37 (2H, t, J=8 Hz, ArH), 7.29 (3H, t, J=7.2 Hz, ArH), 7.20 (2H, t, J=7.6 Hz, ArH), 7.16-7.13 (3H, m, ArH), 6.80 (2H, d, J=8.8 Hz, ArH), 6.57 (2H, d, J=8.8 Hz, ArH), 3.94 (2H, t, J=4.4 Hz, ArOCH2CH2OH), 3.87 (2H, m, ArOCH2CH2OH), 3.42 (2H, t, J=7.2 Hz, ClCH2CH2), 2.92 (2H, t, J=7.2 Hz, ClCH2CH2), 1.95 (1H, t, J=6.4 Hz, OH). 13C-NMR (100 MHz, CDCl3) δ (ppm): 157.2, 143.2, 142.1, 141.3, 2×135.7, 132.2, 130.0, 129.8, 128.8, 128.7, 127.4, 127.0, 113.9, 69.3, 61.8, 43.3, 39.0.
