1478664-02-6

Basic information

• Product Name: EzetiMibe (3R,4R,3'S)-IsoMer
• Synonyms: EzetiMibe (3R,4R,3'S)-IsoMer;(3R,4R)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one;(3R,4R,3'S)-Ezetimibe;Ezetimibe Impurity 30;Ezetimibe Impurity F
• CAS NO: 1478664-02-6
• Molecular Formula: C24H21F2NO3
• Molecular Weight: 409.4252464
• Mol File: 1478664-02-6.mol
• Article Data: 78

Chemical Properties

• Boiling Point: 654.9±55.0 °C(Predicted)
• Appearance: /
• Density: 1.334±0.06 g/cm3(Predicted)
• PKA: 9.72±0.30(Predicted)
• CAS DataBase Reference: EzetiMibe (3R,4R,3'S)-IsoMer(CAS DataBase Reference)
• NIST Chemistry Reference: EzetiMibe (3R,4R,3'S)-IsoMer(1478664-02-6)
• EPA Substance Registry System: EzetiMibe (3R,4R,3'S)-IsoMer(1478664-02-6)

Safety Data

• Hazardous Substances Data: 1478664-02-6(Hazardous Substances Data)

Usage

Description

Ezetimibe (3R,4R,3'S)-IsoMer, also known as Ezetimibe (3'S,3R,4R)-IsoMer, is an impurity found in Ezetimibe (E975000), which is an antihyperlipoproteinemic agent. EzetiMibe (3R,4R,3'S)-IsoMer plays a significant role in the pharmaceutical industry due to its association with cholesterol absorption inhibition.

Uses

Used in Pharmaceutical Industry:
Ezetimibe (3R,4R,3'S)-IsoMer is used as an impurity in the production of Ezetimbe, an antihyperlipoproteinemic agent, for the purpose of cholesterol absorption inhibition. This application is crucial in the treatment of conditions related to high cholesterol levels, which can lead to various health complications such as atherosclerosis and heart disease.
As an impurity in Ezetimbe, the (3R,4R,3'S)-IsoMer may also be subject to regulatory guidelines and quality control measures to ensure the safety and efficacy of the final pharmaceutical product. The presence of this impurity in Ezetimbe could potentially affect the drug's pharmacokinetics, pharmacodynamics, and overall therapeutic outcomes, making it an important consideration in the development and manufacturing process of Ezetimbe-based medications.

Upstream product

• 163222-32-0 (3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone 
• 191330-56-0 [14C]-Sch 57871 
• 873205-85-7 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone hydrate 
• 1197343-05-7 C₄₄H₄₄F₂N₂O₇Si 
• 1232148-26-3 4-((2S,3R)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-oxoazetidin-2-yl)phenyl pivalate 
• 1004520-48-2 (3R,4S)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)azetidin-2-one 
• 1159183-23-9 C₃₂H₂₅F₂NO₅ 
• 1478663-95-4 (S)-3-((R)-2-((S)-(4-((tert-butyldimethylsilyl)oxy)phenyl)((4-fluorophenyl)amino)methyl)-4-(2-(4-fluorophenyl)-5,5-dimethyl-1,3-dioxan-2-yl)butanoyl)-4-phenyloxazolidin-2-one 
• 1593542-72-3 C₃₅H₄₃F₂NO₄Si 
• 128376-64-7 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde 
• 942485-56-5 (S)-3-{4-[2-(4-fluorophenyl)dioxolan-2-yl]butanoyl}-4-phenyl-oxazolidin-2-one 
• 871366-43-7 C₁₉H₂₁BFNO₂ 
• 405-99-2 para-fluorostyrene 
• 190595-64-3 (3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-((E)-3-(4-fluorophenyl)allyl)azetidin-2-one 

Downstream Products

• 1296129-15-1 (2R,3R,6S)-N,6-bis(4-fluorophenyl)-2-(4-hydroxyphenyl)-3,4,5,6-tetrahydro-2H-pyran-3-carboxamide 

Relevant articles and documents

Structural Correction and Process Improvement for Control of a Critical Process Impurity of Ezetimibe

A new process-related impurity of ezetimibe was identified and characterized. The impurity is critical and common to most of the manufacturing routes of ezetimibe. Structural characterization using HMBC indicated the presence of a six-membered ring rather than a nine-membered ring as proposed by the innovator of ezetimibe. Prominently, the existing pharmacopoeial methods for ezetimibe are not capable of detecting this impurity. A control strategy was established by appropriate process control that is capable of purging the impurity to levels comfortably below the regulatory requirement. The formation of the diastereomer impurity during the demonstration of a scale-up batch under the optimized conditions is attributed to epimerization of ezetimibe induced by thermal degradation of the silylating agent.

Preparation method of ezetimibe and intermediate thereof

The invention discloses a preparation method of ezetimibe and an intermediate thereof. The invention provides a preparation method of an ezetimibe intermediate IV. The preparation method comprises thefollowing steps: an ezetimibe intermediate II and an ezetimibe intermediate III are subjected to a cyclization reaction to obtain the ezetimibe intermediate IV in the presence of a trialkylchlorosilane, an organic base, a chiral catalyst and lithium diisopropylamide in an organic solvent, wherein R is methyl, ethyl or propyl. The preparation method is short in route steps, mild in reaction conditions and simple in post-treatment steps, and avoids the connection of a substrate with a chiral group, and the obtained product is high in purity, achieves the standard of bulk drugs, is high in yield, low in production cost, high in atomic utilization rate, and suitable for industrial production.

METHOD OF PREPARING EZETIMIBE AND INTERMEDIATE THEREOF

Disclosed is a method of preparing ezetimibe, including cross-metathesis using a Grubbs 2nd catalyst and deprotection using a Pearlman's catalyst, and an intermediate thereof. The method of preparing ezetimibe is useful as an efficient ezetimibe synthesis technique in pharmaceutical fields using ezetimibe as a raw material.