528565-93-7

Basic information

• Product Name: (S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one
• Synonyms: (S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one;Ezetimibe Impurity 24;(3-[5-(4-Fluoro-phenyl)-5-(R)-hydroxy-pentanoyl]-4-(S)-phenyl-oxazolidin-2-one)
• CAS NO: 528565-93-7
• Molecular Formula: C20H20FNO4
• Molecular Weight: 357.3755032
• Mol File: 528565-93-7.mol

Chemical Properties

• Boiling Point: 572.7±50.0 °C(Predicted)
• Appearance: /
• Density: 1.297±0.06 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 14.17±0.20(Predicted)
• CAS DataBase Reference: (S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one(528565-93-7)
• EPA Substance Registry System: (S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one(528565-93-7)

Safety Data

• Hazardous Substances Data: 528565-93-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one is used as a key intermediate in the synthesis of Ezetimibe, a drug used for treating high cholesterol. Its role in the pharmaceutical industry is vital, as it contributes to the development of medications that help manage and reduce cholesterol levels, thereby lowering the risk of cardiovascular diseases.
Ezetimibe works by inhibiting the absorption of cholesterol in the small intestine, thus reducing the amount of cholesterol in the blood. (S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one (S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one is essential in the production process of this medication, highlighting its importance in the pharmaceutical sector.

Upstream product

• 189028-93-1 (S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione 
• 108-05-4 vinyl acetate 
• 1246853-48-4 (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one 
• 140-11-4 Benzyl acetate 
• 149437-67-2 5-(4-fluorophenyl)-5-oxopentanoic acid methyl ester 
• 108-55-4 glutaric anhydride, 
• 189028-94-2 (S)-5-(4-fluorophenyl)-5-hydroxypentanoic acid 
• 462-06-6 fluorobenzene 
• 149437-76-3 5-(4-fluorophenyl)-5-oxopentanoic acid 
• 793673-93-5 (-)-6-(4-fluorophenyl)tetrahydro-2H-pyran-2-one 
• 67-63-0 isopropyl alcohol 
• 1076200-08-2 3-[5-(4-fluorophenyl)-1,5-dioxopentyl]-4-phenyl-2-oxazolidinone 
• 99395-88-7 (S)-4-phenyl-2-oxazolidinone 

Downstream Products

• 795306-57-9 3′-(S)-4-(S)-3-(R)-[3′-t-butyldimethylsilyloxy-3′-(4-fluorophenyl)propyl]-4-(4-hydroxyphenyl)-1-(4-fluorophenyl)azetidin-2-one 

Relevant articles and documents

Synthesis method of cholesterol absorption selective inhibitor drug intermediate

The invention discloses a synthesis method of a cholesterol absorption selective inhibitor drug intermediate, and is characterized in that the synthesis method comprises the following steps of: dissolving a raw material ezetimibe intermediate (4S)-3-[5-(4-fluorophenyl)-1, 5-dioxopentyl]-4-phenyl-2-oxazolidinone in an organic solvent according to a proper proportion, adding a glucose aqueous solution into the system, rapidly stirring, adjusting the pH to a required value, adding enzyme and coenzyme to continue reaction, controlling the pH of the system in the reaction process until the reaction is finished, adjusting the pH to be acidic after the reaction is finished, extracting, washing with water, concentrating, and evaporating to dryness to remove the solvent, thereby obtaining an oily matter which is a target compound (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxyl valeryl]-4-phenyl-1, 3-oxazacyclopentane-2-ketone. The synthesis method of the cholesterol absorption selective inhibitor drug intermediate has the advantages of being environmentally friendly, high in yield and purity, simple in preparation process, high in economic profit and the like.

Ezetimibe intermediate and preparation method of ezetimibe

The invention relates to an ezetimibe intermediate and a preparation method of ezetimibe. The ezetimibe intermediate has a structure as represented by a formula (I). The preparation method comprises the following steps: providing a compound represented by a formula (II); subjecting the compound as shown in a formula (II) to an asymmetric catalytic hydrogenation reaction under the action of a P-BIAMH catalyst to prepare a compound shown as the formula (I), wherein the P-BIAMH catalyst has a structure as shown in a formula (A) which is described in the specification. In the formula (A), X and Yare halogen independently; R1 is H or a C1-9 alkyl group; R2 is a high-molecular polymer; and a fragment as described in the specification represents a diphosphorus ligand. The method has the advantages of high conversion rate and high safety, and is especially suitable for industrial production.

Crystal form of ezetimibe key intermediate and preparation method of crystal form

The invention provides a crystal form of an ezetimibe key intermediate and a preparation method of the crystal form. The invention relates to the crystal form of (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-2-oxazolidinone and a preparation method thereof. Specifically, the invention provides the crystal form of a compound represented as in a formula (1), and the characteristic diffraction peaks exist in an X-ray powder diffraction pattern at the following 2[theta] angles: 6.195+/-0.2 degrees, 7.640+/-0.2 degrees, 8.289+/-0.2 degrees, 12.847+/-0.2 degrees, 18.394+/-0.2 degrees,19.871+/-0.2 degrees, 21.548+/-0.2 degrees and 25.062+/-0.2 degrees.

According to booklet mai bu synthesis of intermediates method

The invention discloses a according to the method for synthesizing intermediate folds mai bu, comprises the following steps: in under the nitrogen atmosphere, of formula (2) compound are added to in tetrahydrofuran to obtain solution A, A the solution temperature to 5 °C to 10 °C, and to the solution of (-) - A dropping two different pine pinane base chlorine borane, stirring the reaction, after the reaction is finished to obtain solution B, the solution B cooling to - 20 °C to 0 °C, aqueous solution of [...], adjusting solution B of pH=5 - 8, the ethyl acetate extract adjusting pH of the solution B, evaporate ethyl acetate to obtain the residue C, to the remainder of the organic solvent is added in the C, standing, pouring the organic solvent, the residue obtained D, D to the residue in toluene is added to obtain solution E, heating and stirring solution after E, natural cooling, the solution is put into the freezing environment in E, filtering, drying formula (1) compound of the solid, the method is simple and easy, and the cost is low. The reaction is shown as follows:

according to folds Mai Bu and its intermediate synthesis method

The invention provides an Ezetimibe synthesis method comprising the following steps: (a) a compound (5) is subjected to asymmetric reduction reaction to obtain a compound (6), and the compound (6) and tert-butyldimethylsilyl chloride react in an organic solution under the action of alkali to obtain a compound (7); (b) the compound (7) and diisopropylethylamine are dissolved in the organic solution, titanium tetrachloride is added in the organic solution to react at 20-50 DEG C, and a compound (3) is added in the organic solution at minus 20 to minus 60 DEG C to react to obtain a compound (8); (c) the compound (8) and N,O-bis(trimethylsilyl) acetamide react in the organic solution at 20-80 DEG C, tetrabutylammonium fluoride trihydrate is added into the organic solution to react at 20-80 DEG C to obtain a compound (9); (d) the compound (9) is subjected to off-protection reaction to obtain Ezetimibe, wherein R is equal to TBS, Ac or COOCH2CCl3. The invention further provides an Ezetimibe intermediate and a preparation method thereof.

An improved process for preparing according to bookletmai Bu

The invention discloses an improved method for preparing ezetimibe. The method comprises the steps of chirally reducing metal hydride and boride by using a reducing agent; carrying out hydroxy ether protection and condensation reaction by using a one-pot method; and cyclizing, carrying out ether removal protection and the like. The improved method has the advantages that the operation is simple, the reaction selectivity and product stability are good, and the optical purity and yield of the product are high, so that the improved method is suitable for industrial production.

Synthetic method for ezetimibe intermediate

The invention discloses a synthetic method for an ezetimibe intermediate. The synthetic method comprises: by taking a compound I as a raw material, mixing the compound I with a reaction solution; under the action of an acid-binding agent, firstly activating the compound I by pivaloyl chloride; then coupling the compound with S-4-phenyl-2-oxazolidinone; then carrying out reduction reaction through (R)-2-mehtyl-CBS-oxazole borane; and then carrying out post-treatment to prepare (4S)-3-[(5S)-5-(4-fluorophenyl-5-hydroxyl valeryl)-4-phenyl-1,3- azacyclocyclopentane-2-(one) (II), wherein the formula is as shown in the description, and the reaction solution comprises tetrahydrofuran, chloroform, dioxane or dichloromethane. The synthetic method for the ezetimibe intermediate disclosed by the invention has the advantages of being simple to operate, short in synthetic line and relatively low in synthetic cost, and is suitable for large-scaled industrial production.

PROCESS FOR PREPARING EZETIMIBE INTERMEDIATE

The present invention refers to [...] which can inhibit the cholesterol absorption and are (ezetimibe) used in the manufacture of an intermediate manufacturing method relates to compounds of formula 4, a chelatable metal compounds, and metal of formula 2 in one direction so that at step low id id compound of formula 3 to the asymmetrically reducing according to including of the present invention manufacturing method, a method that of the prior art compared to compounds of formula 4 economically, purity can be produced: Said in formula, The X and Ph as defined during specification.

NOVEL PROCESS FOR THE PREPARATION OF EZETIMIBE INTERMEDIATES

The present invention provides a novel process for the preparation of compounds useful as intermediates for the production of Ezetimibe.

Asymmetric synthesis of optically active methyl-2-benzamido-methyl-3-hydroxy-butyrate by robust short-chain alcohol dehydrogenases from Burkholderia gladioli

Three short-chain alcohol dehydrogenases from Burkholderia gladioli were discovered for their great potential in the dynamic kinetic asymmetric transformation of methyl 2-benzamido-methyl-3-oxobutanoate, and their screening against varied organic solvents and substrates. This is the first report of recombinant enzymes capable of achieving this reaction with the highest enantio- and diastereo-selectivity.