An Efficient and Scalable Process for the Synthesis of Antihypercholesterolemic Drug Ezetimibe

An efficient and scalable process for the synthesis of antihypercholesterolemic drug Ezetimibe through chiral Evans auxiliary (S)-4-phenyl-2-oxazolidinone is described. The key steps in this process are the condensation of (S)-3-(5-(4-fluorophenyl)-5,5-dimethoxypentanoyl)-4-phenyloxazolidin-2-one andN-(4-((tert-butyldimethylsilyl)oxy)benzylidene)-4-fluoroaniline, and the stereoselective reduction of Ezetimibe-ketone with NaBH4/I2 which is first applied in the synthesis of Ezetimibe. The process is concise, mild, easy to operate and highly stereoselective (99.6% of de value of Ezetimibe). In addition, Three diastereomers of Ezetimibe are synthesized and served as the referrences in quality control of the product.