The Synthesis Of Eplivanserin And The Isolation Of Its Cis-and Trans-Isomer

Insomnia is a high incidence of mental diseases. With the progress of society, people's pressure increase, and the incidence of insomnia is rising. Eplivanserin is a new hypnotic, which is developed by Sanofi-aventis. Phase III study has showed that the product has good tolerance profile versus placebo, with no residual effect on waking and with no rebound phenomenon or withdrawal symptoms after treatment cessation. The synthetic methods of Eplivanserin were discussed, an optimum route was chosen to low-down the cost, simplify the operating procedure. The study on the catalyst, the proportion of materials and reaction duration showed that when useing 15% HCl as catalyst, the initial proportion of p-Hydroxybenzaldehyde to 2-fluoro- acetophenone was 1.1﹕1, reacting for 30h, the maximal yield was abtained. The O-substituted hydroxylamine was synthesized from N, N-Dimethylethanolamine, the route via chlorine-substituted was superior to bromine- substituted by analyzing and comparing the two routes. The mixture of cis- and trans- eplivanserin was synthesized via 6-step synthetic route, the raw materials were easily gotten, and the operating procedure was simple, the overall yield was 37%. In order to separate the cis- isomer, the methods of adjusting the pH value, Silica gel column chromatography, and reacting with organic acids were tried. We found that the separation via reacting with maleic acid was optimum; the initial yield was 22%.