204589-80-0

Basic information

• Product Name: Methyl (3R,4S)-1-(4-fluorophenyl)-2-oxo-4-[4-(phenylmethoxy)phenyl]-3-azetidinepropanoate
• Synonyms: Methyl (3R,4S)-1-(4-fluorophenyl)-2-oxo-4-[4-(phenylmethoxy)phenyl]-3-azetidinepropanoate;3-Azetidinepropanoic acid, 1-(4-fluorophenyl)-2-oxo-4-[4-(phenylMethoxy)phenyl]-, Methyl ester, (3R,4S)- (REACH);3-Azetidinepropanoic acid, 1-(4-fluorophenyl)-2-oxo-4-[4-(phenylMethoxy)phenyl]-, Methyl ester, (3R,4S)-;1-(4-fluorophenyl)-2-oxo-4-[4-(phenylMethoxy)phenyl]-,Methyl ester,(3R,4S)-3-Azetidinepropanoic acid;Methyl 3-((2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoate;Trans-methyl-3-(((3-[2-oxo-4(benzyloxyphenyl)-1-(4-fluorophenyl)-azetidinone])propionate;Ezetimibe Impurity 18
• CAS NO: 204589-80-0
• Molecular Formula: C₂₆H₂₄FNO₄
• Molecular Weight: 433.47
• EINECS: 1308068-626-2
• Mol File: 204589-80-0.mol

Chemical Properties

• Boiling Point: 628.309 °C at 760 mmHg
• Flash Point: 333.789 °C
• Appearance: /
• Density: 1.238
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.589
• Storage Temp.: 2-8°C
• CAS DataBase Reference: Methyl (3R,4S)-1-(4-fluorophenyl)-2-oxo-4-[4-(phenylmethoxy)phenyl]-3-azetidinepropanoate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl (3R,4S)-1-(4-fluorophenyl)-2-oxo-4-[4-(phenylmethoxy)phenyl]-3-azetidinepropanoate(204589-80-0)
• EPA Substance Registry System: Methyl (3R,4S)-1-(4-fluorophenyl)-2-oxo-4-[4-(phenylmethoxy)phenyl]-3-azetidinepropanoate(204589-80-0)

Safety Data

• Hazardous Substances Data: 204589-80-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Methyl (3R,4S)-1-(4-fluorophenyl)-2-oxo-4-[4-(phenylmethoxy)phenyl]-3-azetidinepropanoate is used as a reagent for the synthesis of antihypercholesterolemia drug ezetimibe. Its unique structure allows it to play a crucial role in the development of this medication, which is designed to help lower cholesterol levels in patients with high cholesterol or other heart disease risk factors.

InChI:InChI=1/C26H24FNO4/c1-31-24(29)16-15-23-25(28(26(23)30)21-11-9-20(27)10-12-21)19-7-13-22(14-8-19)32-17-18-5-3-2-4-6-18/h2-14,23,25H,15-17H2,1H3/t23-,25-/m1/s1

Upstream product

• 1501-26-4 methyl 4-(chlorocarbonyl)butyrate 
• 219653-96-0 (Z)-1-(4-(benzyloxy)phenyl)-N-(4-fluorophenyl)methaneimine 
• 934245-17-7 3-[2-(3-methoxy-3-oxopropyl)-3-(4-fluorophenylamino)-3-(4-benzyloxyphenyl)-1-oxopropyl]-4(S)-phenyloxazolidin-2-one 
• 204589-82-2 (3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 1412967-14-6 (3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-hydroxypropyl)azetidin-2-one 
• 917392-16-6 N-{2-[3-(methoxy)-3-(oxo)-propyl]-3-(4-fluorophenylamino)-3-(4-benzyloxyphenyl)-1-oxo-propyl}-4-(S)-phenyloxazolidin-2-one 

Downstream Products

• 204589-82-2 (3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone 
• 191330-56-0 [14C]-Sch 57871 
• 204589-84-4 3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride 
• 190595-65-4 (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one 
• 204589-68-4 1-(4-fluorophenyl)-(3R)-[(4-fluorophenyl)-(2E)-propenyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone 
• 163222-33-1 ezetemibe 
• 163380-16-3 (3R,4S)-1-(4-fluorophenyl)-3-[(3R)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-azetidin-2-one 
• 163222-32-0 (3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone 
• 163380-15-2 (3R,4S,3'R)-1-(4-fluorophenyl)-4-(4-hydroxyphenyl)-3-[3'-(4-fluorophenyl)-3'-hydroxy-propyl]-azetidin-2-one 
• 163380-20-9 4(S)-(4-acetyloxyphenyl)-3(R)-(3(S)-acetyloxy-3-(4-fluorophenyl)propyl)-1-(4-fluorophenyl)-2-azetidinone 
• 1042722-99-5 methyl 3-[(2S,3R)-1-(4-fluorophenyl)-2-(4-hydroxyphenyl)-4-oxoazetidin-3-yl]propionate 
• 934245-14-4 3-[(2S,3R)-2-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-N-methoxy-N-methylpropaneamide 

Relevant articles and documents

Formal Synthesis of Ezetimibe Using a Proline-mediated, Asymmetric, Three-component Mannich Reaction

The formal total synthesis of ezetimibe was accomplished using a proline-mediated, asymmetric, three-component Mannich reaction as the key step. The two stereogenic centers on the β-lactam skeleton of ezetimibe were controlled by the syn-selective asymmetric Mannich reaction, followed by isomerization.

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.

PREPARATION OF EZETIMIBE

A process for preparing ezetimibe.

IMPROVED PROCESS FOR THE PREPARATION OF EZETIMIBE

The present invention relates to a cost effective and industrially advantageous process for the preparation of (3R,4S)-l-(4-Fluorophenyl)-3-[3(S)-3-(4-fluorophenyl)-3 - hydroxypropyl)]-4-(4-hydroxyρhenyl)-2-azetidinone, referred to here as Ezetimibe, it is represented as formula (1).

Combinations of lipid modulating agents and substituted azetidinones and treatments for vascular conditions

The present invention provides compositions, therapeutic combinations and methods including: (a) at least one lipid modulating agent; and (b) at least one substituted azetidinone or substituted β-lactam sterol absorption inhibitor which can be useful for treating vascular conditions, diabetes, obesity and lowering plasma levels of sterols or 5α-stanols.

Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)- hydroxypropyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone (SCH 58235): A designed, potent, orally active inhibitor of cholesterol absorption

(3R)-(3-Phenylpropyl)-1,(4S)-bis(4-methoxyphenyl)-2-azetidinone (2, SCH 48461), a novel inhibitor of intestinal cholesterol absorption, has recently been described by Burnett et al. and has been demonstrated to lower total plasma cholesterol in man. The potential sites of metabolism of 2 were considered, and the most probable metabolites were prepared. The oral cholesterol-lowering efficacy of the putative metabolites was evaluated in a 7-day cholesterol-fed hamster model for the reduction of serum total cholesterol and liver cholesteryl esters versus control. On the basis of our analysis of the putative metabolite structure-activity relationship (SAR), SCH 58235 (1, 1-4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]- (4S)-(4-hydroxyphenyl)-2-azetidinone) was designed to exploit activity enhancing oxidation and to block sites of potential detrimental metabolic oxidation. Additionally, a series of congeners of 2 were prepared incorporating strategically placed hydroxyl groups and fluorine atoms to further probe the SAR of 2-azetidinone cholesterol absorption inhibitors. Through the SAR analysis of a series of putative metabolites of 2, compound 1 was targeted and found to exhibit remarkable efficacy with an ED50 of 0.04 mg/kg/day for the reduction of liver cholesteryl esters in a 7-day cholesterol-fed hamster model.