Synthesis Of Ezetimibe

As a new type of cholesterol absorption inhibitor,Ezetimibe can inhibit the intestinal absorption of cholesterol in diet and bile.Clinical trails indicate that Ezetimibe has reliable efficacy and less side effects.By referring to relate articles and patents,we used the synthesis route of Ezetimibe which starts from Glutaric anhydride,L-phenylglycine and 4-Fluoroni trobenzene.At the same time,the synthesis of the reactant(S)-(-)-4-phenyl-2-ox azolidinone and 4-[[(4-fluorophenyl)imino]methyl]phenol was completed.There a re nine reactions in the whole systhesis route of Ezetimibe,including Friedel-C rafts acylation,sodium borohydride reduction reaction,asymmetric reduction,hy droxy protection,de-protection of the hydroxy group,cyclization hydrolysis and so on.This article focuses on some unit reactions:(1)Discussed the reaction solvent,reaction temperature,aluminum chloride equivalent in the Friedel-Crafts acylation.When the reaction solvent is methylene chloride,the reaction temperature is 0 ?,anhydrous aluminum chloride equivalent is 2.2eq,the Friedel-Crafts acylation completed well.(2)Discussed the effects of different Lewis acids to sodium borohydride reduction reaction.When the Lewis acid is boron trifluoride etherate,reaction got the highest yield.(3)In amidation reaction,we used an active acid anhydride as the reactive intermediate of the reaction,and when the deacid reagent is 4-dimethylaminop yridine,the reaction completed well.(4)In the asymmetric reduction reaction,we used the catalyst(R)-MeCBS with the equivalent of 0.05eq,and the amount of reducing agent BMS is 2eq.In this condition,reaction achieved the highest yield.(5)In cyclization reaction,we used BSA/TBAF system,when the catalyst TBAF equivalent is 0.01eq,the reaction completed well.