272778-13-9

Basic information

• Product Name: (3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl-3-(trimethylsilyloxy)propyl)-4-(4-(trimethylsilyloxy)phenyl)azetidin-2-one
• Synonyms: (3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl-3-(trimethylsilyloxy)propyl)-4-(4-(trimethylsilyloxy)phenyl)azetidin-2-one;(3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-((trimethylsilyl)-oxy)propyl)-4-(4-((trime;2-Azetidinone, 1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-[(triMethylsilyl)oxy]propyl]-4-[4-[(triMethylsilyl)oxy]phenyl]-, (3R,4S)-;(3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-((trimethylsilyl)-oxy)propyl)-4-(4-((tr
• CAS NO: 272778-13-9
• Molecular Formula: C30H37F2NO3Si2
• Molecular Weight: 553.794
• Product Categories: Ezetimibe intermediates
• Mol File: 272778-13-9.mol

Chemical Properties

• Appearance: /
• Density: 1.118
• Storage Temp.: 2-8°C
• CAS DataBase Reference: (3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl-3-(trimethylsilyloxy)propyl)-4-(4-(trimethylsilyloxy)phenyl)azetidin-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl-3-(trimethylsilyloxy)propyl)-4-(4-(trimethylsilyloxy)phenyl)azetidin-2-one(272778-13-9)
• EPA Substance Registry System: (3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl-3-(trimethylsilyloxy)propyl)-4-(4-(trimethylsilyloxy)phenyl)azetidin-2-one(272778-13-9)

Safety Data

• Hazardous Substances Data: 272778-13-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl-3-(trimethylsilyloxy)propyl)-4-(4-(trimethylsilyloxy)phenyl)azetidin-2-one is used as a potential pharmaceutical candidate due to its unique structure and functional groups. The presence of fluorine and trimethylsilyloxy groups may impart specific biological activities, making it a promising molecule for the development of new drugs.
Used in Organic Synthesis:
(3R,4S)-1-(4-Fluorophenyl)-3-((S)-3-(4-fluorophenyl-3-(trimethylsilyloxy)propyl)-4-(4-(trimethylsilyloxy)phenyl)azetidin-2-one can also be utilized in organic synthesis as a building block or intermediate for the synthesis of more complex molecules. The azetidin-2-one ring and the functional groups present in the molecule can be further modified or used in reactions to create novel compounds with potential applications in various fields.

Upstream product

• 272778-12-8 (4S)-3-[(2R,5S)-5-(4-fluorophenyl)-2-[(S)-[(4-fluorophenyl)amino]({4-[(trimethylsilyl)oxy]phenyl})methyl]-5-[(trimethylsilyl)oxy]pentanoyl]-4-phenyl-1,3-oxazolidin-2-one 
• 189028-95-3 (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidine-2-one 
• 3382-63-6 N-(4-hydroxybenzylidene)-4-fluorobenzenamine 
• 1296129-16-2 3-[(2R,5R)-5-(4-fluorophenyl)-2-[(S)-[(4-fluorophenylamino)(4-hydroxyphenyl)methyl]-5-hydroxy-1-oxo-pentyl]]-4(S)-phenyl-2-oxazolidinone 
• 1185883-40-2 C₃₃H₃₀F₂N₂O₅ 
• 75-77-4 chloro-trimethyl-silane 
• 870634-36-9 methyl 5S-5-(4-fluorophenyl)-5-hydroxyvalerate 

Relevant articles and documents

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.

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.

According to booklet according to booklet mai bu and mai bu intermediates of the synthesis method

The invention relates to an ezetimibe intermediate and a synthesis method of ezetimibe, and mainly solves the technical problems of low yield, low purity, severe conditions and the like in existing methods. According to a technical scheme of the invention, the preparation method includes: subjecting a compound 1 to Aldol condensation reaction under the condition of a self-made isopropoxy titanium trichloride catalyst to generate a compound 2, controlling the Aldol condensation temperature below -5DEG C, in terms of dropwise adding of the catalyst, adding a system A into a catalyst system, conducting ring closing on a compound 2 under the catalysis of TBAF, and removing silicon protecting group under the fluoride salt condition to generate ezetimibe. The synthesis route has mild conditions, the obtained intermediate and end product have high yield, and the purity is high.

A process for the synthesis of intermediate according to booklet of the mai bu and its preparation method and application

The invention discloses an ezetimibe synthesis intermediate and a preparation method and application thereof, the ezetimibe synthesis intermediate has the structure as shown in formula III, and is synthesized by enzyme-chemical method, a chiral hydroxyl compound is produced by asymmetric reduction reaction of a raw material compound under the catalysis effect of aldehyde ketone reductase, and a product can be obtained by cyclization reaction. The ezetimibe synthesis intermediate is used in the preparation of ezetimibe, the process is simple, the concentration of the obtained product is high, and the product has the advantages of high optical purity, mild reaction conditions, environmental friendliness, simple operation, easy industrial amplification, and very good industrial application prospect.

Slurry bed continuous production method of ezetimibe intermediate

The invention discloses a continuous production method of an ezetimibe intermediate 3-[(2R,5S)-5-(4-fluorophenyl)-2-[(S)-[(4-fluorophenyl(amino))][4-R1oxo]phenyl]methyl]-1-oxo-5-[(trimethylsilicon)oxo]phenyl]-4-phenyl-(4S)-2-oxazolidinone. The ezetimibe intermediate is prepared through a contact reaction of raw materials containing a compound A and a compound B with a solid acid catalyst in a slurry bed reactor. The solid acid catalyst is adopted to substitute original titanium tetrachloride and isopropyl titanate catalysts, and a continuous reaction is carried out in the slurry bed reactor, so the method reduces environment pollution and production device requirements, solves the separation and recovery problems of the catalysts, and makes large-scale continuous production of ezetimibe become possible.

Process for the synthesis of azetidinones

A process is provided for preparing azetidinones useful as intermediates in the synthesis of penems and as hypocholesterolemic agents, comprising reacting a β-(substituted-amino)amide, a β-(substituted-amino)acid ester, or a β-(substituted-amino)thiolcarbonic acid ester with a silylating agent and a cyclizing agent selected from the group consisting of alkali metal carboxylates, quaternary ammonium carboxylates, quaternary ammonium hydroxides, quaternary ammonium alkoxides, quaternary ammonium aryloxides and hydrates thereof, or the reaction product of: (i) at least one quaternary ammonium halide and at least one alkali metal carboxylate; or (ii) at least one quaternary ammonium chloride, quaternary ammonium bromide, or quaternary ammonium iodide and at least one alkali metal fluoride, wherein a quaternary ammonium moiety of the cyclizing agent is unsubstituted or substituted by one to four groups independently selected from the group consisting of alkyl, arylalkyl and arylalkyl-alkyl.

PROCESS FOR THE SYNTHESIS OF AZETIDINONES

This invention provides a process for preparing the hypocholesterolemic compound (I) comprising: (a) reacting p-fluorobenzoylbutyric acid with pivaloyl chloride and acylating the product with a chiral auxiliary to obtain a ketone of formula (IV); (b) reducing the ketone of formula (IV) in the presence of a chiral catalyst to an alcohol; (c) reacting the chiral alcohol of step (b), an imine and a silyl protecting agent, then condensing the protected compounds to obtain a beta -(substituted-amino)amide of formula (VII); (d) cyclizing the beta -(substituted-amino)amide of formula (VII) with a silylating agent and a fluoride ion catalyst to obtain a protected lactam of formula (VIII); and removing the protecting groups. The intermediates of formulas (VII and VIII) are also claimed.

METHOD FOR PRODUCING 1,4-DIPHENYL AZETIDINONE DERIVATIVES

The invention relates to a method for producing 1,4-diphenyl azetidinone derivatives from suitably protected β-substituted amino amides, in the presence of silylation agents. Said method uses cyclization catalysts that comprise phosphonium ions as the cation of formula (XII), and ions of the following general formulas (a), (b), (c) or (d) as the anion. In said formulas, the symbols, substituents and indices are defined as follows: Z = C=O, C=S, S=O, SO2 or C=NR20; K = O, S, NR21 or CR22R23; L = NR24 or CR25R26; n = 0 or 1; M = O, C=O, NR27 or CR28R29; Q = O, S, NR30, CR31R32,C=O, C=S, S=O, SO2 or C=NR34; R = CR35 or N; T = CR36 or N; U = CR37 or N; V = CR38 or N; the groups R16 to R19can represent, for example, aryl or (C1-C15) alkyl, aryl(C1-C10)alkene, and the groups R20 to R32 and R34 to R38 can represent in addition H or heteroaryl; R39 and R40 represent, for example (C1-C6) alkyl. The anion can also be R41O-,R42COO- or Cl-, Br- or I- (combined with Ag2O).