Sulfuric Acid → Fenofibrate

Participants

Reaction Conditions

Reaction Steps

465 g (2 mol) of (4-chlorophenyl)(4-hydroxyphenyl)methanone and 815 g (3.9 mol) of the 1-methylethyl ester of 2-bromo-2-methylpropanoic acid (alternative nomenclature: isopropyl 2-bromo-2-methylpropanoate) are introduced into a 4 liter reactor equipped with a stirrer and a condenser. The medium is heated to 120° C. and 265 g (1.92 mol) of potassium carbonate are then added with the aid of a funnel for solids. The reaction medium is subsequently heated for 5 hours at 140°-145° C. and then cooled to about 100° C. It is subsequently diluted with aqueous isopropyl alcohol and then acidified with sulfuric acid. The reaction medium is then cooled to 18°-20° C. in order to crystallize the product, which is filtered off and washed with sodium hydroxide solution and then water. The product is recrystallized from isopropanol to give 605 g of fenofibrate (yield=83.9%) with a purity greater than 99.5% (determination by high pressure liquid chromatography, abbreviated to HPLC).

Provenance & Evidence