Isopropanol → Fenofibrate

Participants

Reaction Conditions

Reaction Steps

100 g (0.43 mol) of (4-chlorophenyl)(4-hydroxyphenyl)methanone and 165 g (0.79 mol) of the 1-methylethyl ester of 2-bromo-2-methylpropanoic acid are introduced, under a nitrogen atmosphere, into a 3-necked round-bottomed flask equipped with a stirrer and a condenser. The reaction medium is heated to 110° C. and a solution of 50 g (0.36 mol) of potassium carbonate in 50 ml of demineralized water is then added slowly over a period of 20 minutes, with distillation taking place at 100° C. The distillate separates out into 2 phases. The lower phase is recycled into the reaction medium. After heating at 110°-112° C. for 1.5 h, the reaction medium is brought to 140° C. and a temperature of 140°-145° C. is maintained for 4 hours. The reaction medium is then cooled to about 90° C. and 210 ml of 80% isopropyl alcohol are added. The mixture is then left to cool for 12 h, with stirring, after which the suspension obtained is filtered at 0° C. The precipitate is washed with 4 times 200 ml of demineralized water and then recrystallized from propan-2-ol to give 119.5 g (yield=77%) of fenofibrate.

Provenance & Evidence