1478664-18-4

Usage

Uses

Used in Pharmaceutical Industry:
(3S,4S)-1-(4-fluorophenyl)-3-((R)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one is used as an intermediate in the synthesis of (3S,4S,3'S)-Ezetimibe (E975040), which is a 3-epimer impurity of Ezetimibe (E975000). Ezetimibe is a cholesterol absorption inhibitor, making (3S,4S)-1-(4-fluorophenyl)-3-((R)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one significant in the development of treatments for hypercholesterolemia and related cardiovascular conditions.
Used in Chemical Synthesis:
(3S,4S)-1-(4-fluorophenyl)-3-((R)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one can also be utilized in the chemical synthesis of various other pharmaceuticals and organic compounds due to its unique structure and functional groups. Its fluorophenyl and hydroxyphenyl moieties can be exploited in the creation of new molecules with potential applications in different industries, such as agrochemicals, materials science, and more.

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 
• 954109-26-3 (3R,4S)-4-(4-(trimethylsilyloxy)phenyl)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one 
• 190595-65-4 (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one 
• 70627-52-0 4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine 
• 221349-58-2 (2S,3S)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxazetidine-3-carbaldehyde 
• 221349-56-0 (3S,4S)-4-(4-Benzyloxy-phenyl)-3-((S)-1,2-dihydroxy-ethyl)-1-(4-fluoro-phenyl)-azetidin-2-one 
• 221349-60-6 (3R,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[(E)-3-(4-fluoro-phenyl)-3-oxo-propenyl]-azetidin-2-one 
• 231301-00-1 (3S,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[3-(4-fluoro-phenyl)-1-hydroxy-3-oxo-propyl]-azetidin-2-one 
• 942485-60-1 (3R,4S)-4-{4-[(tert-butyldimethylsilyl)oxy]phenyl}-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one 
• 1042722-68-8 C₄₃H₃₅F₂NO₃ 
• 1159183-24-0 benzyl (4-((2S,3R)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-oxoazetidin-2-yl)phenyl) carbonate 
• 1232148-26-3 4-((2S,3R)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-oxoazetidin-2-yl)phenyl pivalate 
• 1159183-23-9 C₃₂H₂₅F₂NO₅ 

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 
• 851860-30-5 (1S)-1-(4-fluorophenyl)-3-[(3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-{[(trifluoromethyl)sulfonyl]oxy}-phenyl)azetidin-3-yl]propyl acetate 
• 852204-12-7 (1S)-1-(4-fluorophenyl)-3-[(2S,3R)-1-(4-fluorophenyl)-2-(3'-hydroxybiphenyl-4-yl)-4-oxoazetidin-3-yl]propyl acetate 

Relevant academic research and scientific papers

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.

Preparation method of ezetimibe optical isomer

The invention relates to a preparation method of an ezetimibe optical isomer, and concretely relates to a method for synthesizing an ezetimibe impurity L by using a compound 03. The method comprises the following steps: 1) mixing the compound 03 with a silyl ether protecting group, 2) adding methyl tert-butyl ether, and 3) adding alcohol and acid.

Preparation method of ezetimibe SSS isomer

The invention relates to a preparation method of an ezetimibe SSS isomer. Specifically, the preparation method is used for producing the ezetimibe SSS cis-isomer by use of an RSS intermediate as a starting raw material and by virtue of Mitsunobu reaction and deprotection. The preparation method of the ezetimibe SSS isomer is simple in process steps, and the obtained product is good in yield and high in purity.

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.

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.

Study on the HPLC-based separation of some ezetimibe stereoisomers and the underlying stereorecognition process

The enantioseparation of ezetimibe stereoisomers by high-performance liquid chromatography on different chiral stationary phases, ie, 3 polysaccharide-based chiral columns, was studied. It was observed that cellulose-based Chiralpak IC column exhibited the best resolving ability. After the optimization of mobile phase compositions in both normal and reversed phase modes, satisfactory separation could be obtained on Chiralpak IC column, especially in normal phase mode. The use of prohibited solvents as nonstandard mobile phase gave rise to better resolution than that of standard mobile phases (n-hexane/alcohol system). In addition, the presence of ethanol in nonstandard mobile phase has played an important role in enhancing chromatographic efficiency and resolution between ezetimibe stereoisomers. Various attempts were made to comprehensively compare the chiral recognition capabilities of immobilized versus coated polysaccharide-based chiral columns, amylose-based versus cellulose-based chiral stationary phases, reversed versus normal phase modes, and standard versus nonstandard mobile phases. Moreover, possible solute-mobile phase-stationary phase interactions were derived to explain how stationary and mobile phases affected the separation. Then the method validation with respect to selectivity, linearity, precision, accuracy, and robustness was carried out, which was demonstrated to be suitable and accurate for the quantitative determination of (RRS)-ezetimibe impurity in ezetimibe bulk drug.

Preparation method of ezetimibe for treating hyperlipidemia

The invention discloses a preparation method of ezetimibe for treating hyperlipidemia, and belongs to the field of drug synthesizing. The method is characterized in that a compound 2 is treated as theraw material and subjected to four synthesizing steps to prepare ezetimibe 1, wherein the four steps include the step of protection for carbonyl group, cyclizing, carbonyl reduction and hydrogenationdeprotection. Compared with methods in existing documents, the preparation method has the advantages that the use of polluting titanium agents is avoided; the synthesizing steps are decreased; the technology stability is improved; massive production can be performed.

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.

Preparation method of medicine ezetimibe for treating hyperlipidemia

The invention discloses a preparation method of a medicine ezetimibe for treating hyperlipidemia, belonging to the field of pharmaceutical synthesis. According to the preparation method, a compound 2is taken as a raw material, and the ezetimibe 1 is prepared by four steps of carbonyl protection, cyclization, carbonyl reduction and oxidation. Compared with the existing method reported by documents, the preparation method provided by the invention avoids the use of a polluting titanium reagent, and is fewer in synthesis steps, higher in process stability and suitable for large-scale production.

Preparation method of ezetimibe serving as drug for treating hyperlipidemia

The invention discloses a preparation method of ezetimibe serving as a drug for treating hyperlipidemia and belongs to the field of drug synthesis. Ezetimibe 1 is prepared by carrying out four synthesis steps including carbonyl protection, cyclization, carbonyl reduction and deprotection on a compound 2 serving as a raw material. Compared with a method reported by an existing document, the preparation method is capable of avoiding using a polluting titanium reagent and reducing the synthesis steps, higher in process stability and suitable for large-scale production.