1240815-99-9

Upstream product

• 4397-53-9 p-benzyloxybenzaldehyde 
• 406-00-8 4-fluoro-N-hydroxyaniline 
• 1206694-75-8 4-(2-aza-2-(4-fluorophenyl)vinyl)-1-benzyloxybenzene 
• 415960-63-3 N-(4-(benzyloxy)benzyl)-4-fluoroaniline 
• 100-44-7 benzyl chloride 
• 123-08-0 4-hydroxy-benzaldehyde 
• 350-46-9 4-Fluoronitrobenzene 

Downstream Products

• 1240816-36-7 (3R,4S)-4-(4-(benzyloxy)phenyl)-3-((4'R)-2',2'-dimethyl-1',3'-dioxolan-4'-yl)-1-(4-fluorophenyl)azetidin-2-one 
• 1240816-39-0 (3R,4S)-4-(4-(benzyloxy)phenyl)-3-((1'R)-1',2'-dihydroxyethyl)-1-(4-fluorophenyl)-azetidin-2-one 
• 1240816-59-4 (3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-formyl-azetidin-2-one 
• 221349-58-2 (2S,3S)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxazetidine-3-carbaldehyde 
• 1316784-95-8 C₂₇H₂₆FNO₄ 
• 1316784-92-5 C₂₇H₂₆FNO₄ 
• 1316784-90-3 C₂₇H₂₆FNO₄ 
• 1415704-24-3 C₃₁H₂₈FNO₃ 
• 1415704-53-8 C₃₁H₂₈FNO₃ 
• 1415704-54-9 C₃₁H₂₈FNO₃ 
• 1415704-55-0 C₃₁H₂₈FNO₃ 
• 1415704-58-3 C₂₅H₂₄FNO₄ 
• 1415704-27-6 C₃₁H₃₆FNO₄Si 
• 1415704-20-9 C₂₈H₂₈FNO₄ 

Relevant academic research and scientific papers

Total synthesis of ezetimibe, a cholesterol absorption inhibitor

Ezetimibe (1), a strong β-lactamic cholesterol absorption inhibitor, was synthesized from (R)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one 7. Independent pathways were analyzed in order to select the optimal one, which involved 1,3-dipolar cycloaddition with C-(4-benzyloxyphenyl)-N-(4-fluorophenyl) -nitrone (8), intramolecular nucleophilic displacement at the benzylic position of the lactone, cleavage of the N-O bond, elimination of a water molecule, hydrogenation of the double bond, rearrangement of the six-membered lactone ring into a β-lactam moiety, and final deprotection of the phenolic hydroxyl group. Highly stereoselective Sc(OTf)3-catalyzed 1,3-dipolar cycloaddition was the most crucial step of the synthesis. Owing to the rigid transition state of the cycloaddition, the absolute configuration of the starting lactone controlled the formation of other stereogenic centers of the final molecule 1.

A formal synthesis of ezetimibe via cycloaddition/rearrangement cascade reaction

A formal synthesis of a powerful cholesterol inhibitor, ezetymibe 1, is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from acetonide of l-glyceraldehyde and suitable C,N-diarylnitrone. The adduct with (3R,4S) configuration at the azetidinone ring, obtained with high stereoselectivity, was subsequently subjected to deprotection of the diol side chain followed by glycolic cleavage and base-induced isomerization at the C3 carbon atom to afford the (3S,4S) aldehyde, which has been already transformed into ezetimibe by the Schering-Plough group.

A PROCESS FOR THE PREPARATION OF AN ALDEHYDE BETA-LACTAM COMPOUND

The invention relates to a process for the preparation of an aldehyde beta-lactam compound of formula (I), wherein P1 is H or a protecting group, useful in the preparation of ezetimibe, from a nitrone compound of formula (II). The nitrone compound Il is prepared by reacting 4-fluorophenylhydroxyloamine with OH- protected 4-hydroxybenzaldehyde. The nitrone compound of formula (II) is reacted with an acetylene compound of formula (III) to form a compound of formula (IV), and the compound of formula (IV), after optional deprotection, is oxidized to obtain an aldehyde of formula (V), which undergoes isomerisation to the compound of formula (I). The subject of the invention are also novel compounds of formulas (II) and (IV).