204589-82-2

Basic information

• Product Name: (3R,4S)-1-(4-Fluorophenyl)-2-oxo-4-[4-(benzyloxy)phenyl]-3-azetidinepropanoic acid
• Synonyms: (3R,4S)-1-(4-Fluorophenyl)-2-oxo-4-[4-(benzyloxy)phenyl]-3-azetidinepropanoic acid;3-Azetidinepropanoic acid, 1-(4-fluorophenyl)-2-oxo-4-[4-(phenylMethoxy)phenyl]-, (3R,4S)-;1-(4-fluorophenyl)-2-oxo-4-[4-(phenylMethoxy)phenyl]-, (3R,4S)-3-Azetidinepropanoic acid;3-((2S,3R)-2-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoic acid;Ezetimibe Impurity 13;3-[(3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-phenylmethoxyphenyl)azetidin-3-yl]propanoic acid
• CAS NO: 204589-82-2
• Molecular Formula: C₂₅H₂₂FNO₄
• Molecular Weight: 419.44
• EINECS: 1308068-626-2
• Mol File: 204589-82-2.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 687.445 °C at 760 mmHg
• Flash Point: 369.553 °C
• Appearance: /
• Density: 1.292
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.614
• Storage Temp.: 2-8°C
• PKA: 4.53±0.10(Predicted)
• CAS DataBase Reference: (3R,4S)-1-(4-Fluorophenyl)-2-oxo-4-[4-(benzyloxy)phenyl]-3-azetidinepropanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4S)-1-(4-Fluorophenyl)-2-oxo-4-[4-(benzyloxy)phenyl]-3-azetidinepropanoic acid(204589-82-2)
• EPA Substance Registry System: (3R,4S)-1-(4-Fluorophenyl)-2-oxo-4-[4-(benzyloxy)phenyl]-3-azetidinepropanoic acid(204589-82-2)

Safety Data

• Hazardous Substances Data: 204589-82-2(Hazardous Substances Data)

Usage

Uses

(3R,4S)-1-(4-Fluorophenyl)-2-oxo-4-[4-(benzyloxy)phenyl]-3-azetidinepropanoic Acid is a reagent for the synthesis of antihypercholesterolemia drug Ezetimibe. Also a reagent for the preparation of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone (SCH 58235) designed as inhibitor of cholesterol absorption.

InChI:InChI=1/C25H22FNO4/c26-19-8-10-20(11-9-19)27-24(22(25(27)30)14-15-23(28)29)18-6-12-21(13-7-18)31-16-17-4-2-1-3-5-17/h1-13,22,24H,14-16H2,(H,28,29)/t22-,24-/m1/s1

Upstream product

• 1046809-85-1 3-[(2S,3R)-2-(4-benzyloxy-phenyl)-1-(4-fluorophenyl)-4-oxo-azetidin-3-yl]-propionic acid benzyl ester 
• 1412967-14-6 (3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-hydroxypropyl)azetidin-2-one 
• 219653-96-0 (Z)-1-(4-(benzyloxy)phenyl)-N-(4-fluorophenyl)methaneimine 
• 204589-80-0 methyl 3-((2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoate 

Downstream Products

• 190595-65-4 (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one 
• 934245-14-4 3-[(2S,3R)-2-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-N-methoxy-N-methylpropaneamide 
• 204589-80-0 methyl 3-((2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoate 
• 1412967-14-6 (3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-hydroxypropyl)azetidin-2-one 

Relevant articles and documents

Synthesis and Evaluation of 2-Azetidinone and 1H-Pyrrole-2,5-dione Derivatives as Cholesterol Absorption Inhibitors for Reducing Inflammation Response and Oxidative Stress

Excess lipid accumulation can initiate the development and progression of atherosclerotic lesions, thus eventually leading to cardiovascular disease. Lipid-lowering medication therapy is one of the cornerstones of cardiovascular disease therapy. On the basis of the cholesterol absorption inhibitor ezetimibe, we successfully synthesized seven 2-azetidinone derivatives and eighteen 1H-pyrrole-2,5-dione derivatives. Most of the new compounds significantly inhibited cholesterol uptake in vitro. In addition, one of the most active inhibitors, 3-(4-fluorophenyl)-1-[(3S)-3-hydroxy-3-(4-hydroxyphenyl)propyl]-4-(4-hydroxyphenyl)-1H-pyrrole-2,5-dione (14q), showed no cytotoxicity in L02 and HEK293T cell lines. Further evaluation indicated that 14q inhibited considerably the amount of TNF-α, ROS, MDA, and LDH in vitro. Therefore, 14q might be a novel cholesterol absorption inhibitor.

An improved and scalable process for the synthesis of ezetimibe: An antihypercholesterolemia drug

An efficient, cost-effective and large-scale synthesis of ezetimibe 1, an antihypercholesterolemia drug, is described. Chiral oxazolidinone chemistry was used to fix the required stereochemistry of the β-lactam ring, and the chiral oxazaborolidine chemistry was used to fix the hydroxyl group stereochemistry. The synthesis significantly lowers the cost and provides easy access to ezetimibe on large scale.

IMPROVED PROCESS FOR THE PREPARATION OF EZETIMIBE AND ITS INTERMEDIATES

The present invention provides an improved process for the preparation of ezetimibe through novel organic amine salt compounds of general formula (1). The present invention also relates to a highly pure ezetimibe and 3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl) azetidin-3-yl)propionic acid compound.