反应详情

1 kg (3.14 mol) of fenofibric acid (II), 500 ml of dimethyl sulfoxide and 1 l of isopropyl acetate were charged into a jacketed 5 l reactor under nitrogen. 433.5 g (3.14 mol) of potassium carbonate were then added, with stirring at ambient temperature, and the reaction mixture was brought to 85-90° C. for 45 min. The temperature of the reaction mixture was subsequently reduced to approximately 80° C. and 354 ml (3.77 mol) of 2-bromopropane and then 100 ml of isopropyl acetate were added over a period of 50 min. The mixture was kept stirring at 85-95° C. for 5 hours and then slightly cooled to approximately 80° C. In-process monitoring showed that the degree of conversion to give fenofibrate was approximately 99.5%. The content of the reactor was hot-filtered and the salts separated on the filter were washed with 1 l of isopropyl acetate, which was combined with the filtrate. The isolated salts, which essentially comprise potassium bromide, were dried and kept for recycling. The filtrate was concentrated under reduced pressure while maintaining a bulk temperature of approximately 80° C., and of 95° C. at the end of concentrating. After removal of the solvents, 2.27 l of isopropanol and 455 ml of pure water were added. The mixture was brought to gentle reflux for 10 min and then hot-filtered. Under stirring, the filtrate was slowly cooled down to a temperature of 0° C. The crystallized fenofibrate was separated by filtration on a filtering device, washed on the filtering device with approximately 500 ml of ice-cold isopropanol and then dried under vacuum at 45-50° C. 1075 g of fenofibrate with a purity of greater than 99.5% and comprising no impurity at a level of greater than 0.05% were thus obtained (yield=94.9%).

1. customwas subsequently reduced to approximately 80° C.
2. stirringThe mixture was kept stirring at 85-95° C. for 5 hours
3. temperatureslightly cooled to approximately 80° C