190595-65-4Relevant articles and documents
METHOD OF PREPARING EZETIMIBE AND INTERMEDIATE THEREOF
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Paragraph 0074-0076, (2019/08/30)
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.
Preparation method of ezetimibe intermediate
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Paragraph 0043; 0046; 0050; 0054, (2018/07/30)
The invention provides a preparation method of an ezetimibe intermediate I. The preparation method includes: (1), in an inert solvent and at the presence of alkali, enabling a compound shown as a formula III to react with fluoroacetophenone to obtain a compound shown as a formula II; (2), providing a mixed solution A of hexamethyl disilicon sodium amide and an organic solvent; (3), enabling the compound shown as the formula II to react with the mixed solution A to obtain a compound shown as a formula I. The method can be completed at room temperature, reaction yield is increased to about 90% from 70% of the prior art, reactant purity is improved greatly, and a condition is provided for realizing industrial production of ezetimibe.
METHOD FOR PRODUCING DIPHENYL AZETIDINE DERIVATIVE
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Paragraph 0028; 0030, (2018/07/31)
PROBLEM TO BE SOLVED: To provide a highly efficient industrial production method of a diphenyl azetidine derivative which is a production raw material of a β-lactam derivative useful for the treatment and prevention of hypercholesterolemia such as arteriosclerosis. SOLUTION: There is provided a method for producing a compound represented by the general formula (III) [wherein, R is the same as the case of the general formula (I)] by reacting a compound represented by the general formula (I) [wherein, R represents a lower alkyl group which may be branched, an ally group, a lower alkyl group including a lower alkoxy group, a lower alkyl group including a lower thioalkyl group, a tetrahydropyranyl group, a triphenylmethyl group, a silyl group having a substituent, a phenyl group which may have a substituent and a benzyl group which may have a substituent.] and a compound represented by the general formula (II) [wherein, M represents MgCl, MgBr, MgI or Li) in a toluene solvent. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
Preparation method of ezetimibe for treating hyperlipidemia
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Paragraph 0021; 0024; 0032; 0039, (2018/03/25)
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.
Ezetimibe intermediate, synthesis method of intermediate and synthesis method of ezetimibe
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Paragraph 0054; 0101; 0102, (2017/07/01)
The invention provides an ezetimibe intermediate, a synthesis method of the intermediate and a synthesis method of ezetimibe. The method is short in synthetic route. The method includes the steps of making fluorobenzene as the initial raw material sequentially have acylation reaction with glutaric anhydride and 4(S)-4-phenyl oxazolidinone to generate a compound II, protecting carbonyl through 2,2-bis-substituted-1,3-propylene glycol to obtain a compound III, generating a compound V through the compound III and a compound IV under the catalysis of titanium tetrachloride, cyclizing the compound V to generate a compound VI, hydrolyzing the compound VI to obtain a compound VII, and reducing the compound VII through a borane chiral reducing agent and removing a benzyl protecting group in a hydrogenated mode to obtain the ezetimibe. The method is high in yield, little in side reaction and suitable for industrial mass production.
MANUFACTURING METHOD OF (3R,4S)-1-(4-FLUOROPHENYL)-[3(S)-HYDROXY-3-(4-FLUOROPHENYL)PROPYL]-[4-(PHENYLMETHOXY)PHENYL]-2-AZETIDINONE
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, (2017/11/18)
PROBLEM TO BE SOLVED: To provide a method for effectively manufacturing high purity (3R,4S)-1-(4-fluorophenyl)-[3(S)-hydroxy-3-(4-fluorophenyl)propyl]-[4-(phenylmethoxy)phenyl]-2-azetidinone with reduced contents of specific impurities and enantiomers. SOLUTION: When a benzyl protective body is manufactured by reacting a benzyl protective keto body and borane in presence of a CBS catalyst, the benzyl protective keto body is injected under a condition with co-existing a part of borane of needed amount in a reaction system in advance and remaining borane is added later to conduct the reaction. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
Preparation method of azetidinone derivatives
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Paragraph 0058; 0059; 0060, (2016/12/01)
The invention discloses a preparation method of azetidinone derivatives. The preparation method comprises that a compound I undergoes a benzoylation reaction to produce an intermediate A, the intermediate A is hydrolyzed to form an intermediate B and the intermediate B undergoes a decarboxylic reaction to produce an azetidinone derivative. The preparation method has a simple synthesis route, utilizes cheap and easily available industrial products as raw materials, has simple reaction processes and simple treatment processes, can produce ezetimibe in a short production period, directly utilizes intermediate crude products for the next reaction process, has a high technology serialization degree and greatly improves a total yield.
Synthesis method of ezetimibe
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Paragraph 0025-0039, (2016/10/31)
The invention discloses a synthesis method of ezetimibe, which comprises the following steps: under the protection of inert gas, adding N,O-dimethylhydroxylamine hydrochloride and EZE-5 into a solvent, and dropwisely adding a DEAC toluene solution to react, thereby obtaining EZE-15; adding magnesium chips and THF (tetrahydrofuran), and dropwisely adding a 4-fluorobromobenzene THF solution to obtain oily EZE-8; adding ethyl benzene, and stirring; dropwisely adding a prepared triethylamine-formic acid mixed reagent, and adding a catalyst to react, thereby obtaining EZE-9; adding THF and EtOH, stirring, adding 5% Pd/C, replacing air in a reaction bulb with high-purity nitrogen, introducing high-purity hydrogen, and carrying out LC until the reaction is complete, thereby obtaining a crude product EZE-10; and refining the crude product with isopropanol and water to obtain the white crystalline powder high-purity EZE-10. The method has the advantages of high synthesized ezetimibe purity, simple used equipment, simplified steps and low production cost, and is suitable for industrial production.
PROCESS FOR SYNTHESIS OF EZETIMIBE AND INTERMEDIATES USED IN SAID PROCESS
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, (2015/06/03)
A process for the production of ezetimibe and intermediates used in said process are disclosed. A kind of Morita-Baylis-Hillman adduct can be altered to chiral carboxylic acid derivatives of β-arylamino α-methylene with high activity and selectivity by means of ally lamination reaction, and the above carboxylic acid derivatives of β-arylamino α-methylene can be altered to the chiral intermediates of ezetimibe by means of simple conversion and further synthesized into the chiral drug ezetimibe. The synthesis route introduces chirality through the use of a chiral catalysis method, thereby avoiding the use of the chiral auxiliary oxazolidinone; and the route is economical and eco-friendly.
PROCESS FOR SYNTHESIS OF EZETIMIBE AND INTERMEDIATES USED IN SAID PROCESS
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Paragraph 0177; 0178, (2015/06/24)
A process for the production of ezetimibe and intermediates used in said process are disclosed. A kind of Morita-Baylis-Hillman adduct can be altered to chiral carboxylic acid derivatives of β-arylamino α-methylene with high activity and selectivity by means of ally lamination reaction, and the above carboxylic acid derivatives of β-arylamino α-methylene can be altered to the chiral intermediates of ezetimibe by means of simple conversion and further synthesized into the chiral drug ezetimibe. The synthesis route introduces chirality through the use of a chiral catalysis method, thereby avoiding the use of the chiral auxiliary oxazolidinone; and the route is economical and eco-friendly.
