133921-27-4

Example 25: Synthesis of (E)-4-((2-(4-((Z)-1-(4-hydroxyphenyl)-2-phenylbut-1-en-1-yl)-3-methylphenoxy)ethyl)amino)-N,N-dimethylbut-2-enamide Step-1: Synthesis of 4-iodo-3-methylphenol 4-Amino-3-methylphenol (10 g, 81 mmol) was dissolved in THF (45 mL) and cooled to 0°C. Under stirring, 3M HCl (35 mL) was slowly added, followed by NaNO2 (6.1 g, 89 mmol), and the reaction was carried out for 10 min. Next, an aqueous solution of potassium iodide (53.89 g, 166 mmol) (140 mL) was added dropwise to the reaction mixture, and stirring was continued for 15 min by keeping 0°C. After completion of the reaction, the reaction mixture was extracted with EtOAc. The organic layer was washed with water and brine sequentially and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (230-400 mesh) to afford the title compound 4-iodo-3-methylphenol (9 g, 47% yield) using 10% EtOAc in hexane solution as eluent.

[1] Patent: WO2016/196342, 2016, A1. Location in patent: Page/Page column 129
[2] Patent: US6689922, 2004, B1. Location in patent: Page column 85
[3] Journal of the Chemical Society, 1951, p. 1184,1186
[4] Patent: US6562823, 2003, B1