Patent ID: 8013150

Claim:
A process for the preparation of (3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-2-azetidinone (Ezetimibe) compound of formula (I) comprising: (a) reacting glutaric anhydride compound of formula (II) with linear or branched chain aliphatic C1-C6 alcohols in presence of a base to give alkyl ester compound of formula (III) wherein R is C1-C6 alkyl; (b) reacting the compound of formula (III) with pivaloyl chloride in presence of an acid trapping agent, and subsequently reacting the product with a chiral auxiliary compound of formula (IV) to give ester compound of formula (V) (c) reacting the ester compound of formula (V) with benzylated imine compound of formula (VI) in presence of a Lewis acid to obtain an amide compound of formula (VII) (d) cyclizing the amide compound of formula (VII) with (i) a silylating agent and (ii) a fluoride ion catalyst cyclizing agent in a solvent to obtain the compound of formula (VIII) (e) hydrolyzing the ester group of compound of formula (VIII) with a base in a solvent, followed by adjusting the pH of the reaction mixture to 5-7, and followed by extracting the carboxylic acid compound of formula (IX) (f) reacting the compound of formula (IX) with oxalyl chloride in a first solvent to form an acid chloride product, followed by reacting the product acid chloride compound in situ with 4-fluorophenyl zinc halide in the presence of palladium(II) acetate in a second solvent, thereby producing the aromatic ketone compound of formula (X) (g) reducing the aromatic ketone compound of formula (X) in presence of a chiral reducing agent alone or in combination with a chiral catalyst in a solvent to obtain hydroxy compound of formula (XI), followed by isolating the hydroxy compound of formula (XI) as a solid using an organic solvent, (h) debenzylating the compound of formula (XI) with palladium carbon in an alcoholic solvent or dichloromethane or toluene to produce the compound of formula (I)