- Synthetic method for rosuvastatin intermediate
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The invention discloses a synthetic method for a rosuvastatin intermediate and belongs to the field of medicine. The rosuvastatin intermediate is (3R)-tert-butyl dimethyl siloxyl-5-oxo-6-methyl triphenylphosphine caproate. According to the invention, (R)-3-tert-butyl dimethyl siloxyl-5-(1H-imidazole-1-group)-5-methyl oxoglutarate compound is taken as a raw material, is condensed with 5-methylsulfonyl-1-phenyl-1H-tetrazole and then reacts with phosphorus triphenyl oxide, so as to generate the (3R)-tert-butyl dimethyl siloxyl-5-oxo-6-methyl triphenylphosphine caproate. According to the invention, 5-methylsulfonyl-1-phenyl-1H-tetrazole is utilized to condense, so that the intermediate is stable; the detection is convenient; the phosphorus triphenyl oxide instead of triphenyl phosphine is usedas the raw material, so that the side product phosphorus triphenyl oxide of wittig reaction can be recycled; the process is simple and easy for industrialization.
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Paragraph 0035-0040
(2019/01/08)
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- Preparation method of high-purity statin drug intermediate
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The invention relates to a preparation method of a high-purity statin drug intermediate. The preparation method is characterized in that 3-hydroxyl ethyl glutarate is used as the initial raw material to prepare (3R)-tert-butyl dimethyl silyloxy-5-oxo-6-triphenyl phosphine caproate (abbreviated as J6) through substitution reaction, hydrolysis reaction, cyclization reaction, resolution reaction, hydrogenation reaction, acylation reaction and Wittig reaction. The preparation method is mild in condition, stable in process, cheap in raw material, easy in raw material obtaining, easy in three-waste treatment, low in preparation cost, high in product purity and suitable for industrial production.
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- Preparation method of novel rosuvastatin calcium intermediate
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The invention provides a preparation method of a novel rosuavastatin calcium intermediate I which is suitable for industrial large-scale production. The preparation method comprises the step of enabling triphenyl methyl phosphorus bromide to react with a compound II, thus obtaining an intermediate I. The preparation method provided by the invention is safe and simple and is strong in operability, and a final finished product which is high in efficiency and purity can be obtained.
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Paragraph 0063; 0064; 0065; 0066; 0067; 0068; 0069-0083
(2017/08/29)
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- Preparation method for rosuvastatin calcium intermediate
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The invention discloses a preparation method for a rosuvastatin calcium intermediate. The preparation method comprises the following steps: adding Salen Co (III) in a sodium acetylide tetrahydrofuran solution, dropwise adding epichlorohydrin for reaction, dropwise adding a product into a sodium cyanide aqueous solution for reaction to obtain a product, and dropwise adding the obtained product into methanol and introducing hydrogen chloride to obtain (3R)-hydroxyl-methyl 5-octynoate (III); with dichloromethane as a solvent, adding the compound (III) and tert-butyldimethylsilyl chloride to obtain a compound (IV), dropwise adding the compound (IV) into a sodium hypochlorite aqueous solution to obtain 6-chloro-(R)-(+)-3-(tert-butyldimethylsilanyloxy)-5-oxo-methyl caproate (V); with 2-methyltetrahydrofuran as a solvent, adding 6-chloro-(R)-(+)-3-(tert-butyldimethylsilanyloxy)-5-oxo-methyl caproate and triphenylphosphine so as to obtain methyl (3R)-(tert-butyldimethylsilanyloxy)-5-oxo-6-triphenylphosphoranylidenehexanoate(VI). According to the preparation method provided by the invention, the raw materials are simple, the reaction conditions are mild, environment friendliness is realized and the preparation method can be used for industrial mass production.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF HMG-COA REDUCTASE INHIBITOR INTERMEDIATES
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The present invention relates to novel processes for the preparation of compounds of Formula-II useful as intermediates in preparation of HMG-CoA reductase inhibitors, and further conversion of said intermediates to HMG-CoA reductase inhibitors. The process for the preparation of compounds of Formula-II comprises reacting compounds of Formula-Ill with dimethylformamide dimethylacetal in the presence of a base to get compounds of Formula-IV, reacting the compounds of formula-IV with alkyl chloroformate in the presence of a base to get compounds of Formula-V, and converting the compounds of Formula-V into compounds of Formula-II. The compounds have the following structures, [Formulas should be inserted here] wherein X is hydrogen or hydroxy protecting group, R1 is carboxyl protecting group, Alk represents C1-C4 alkyl and R2, R3 and R4 are independently selected from substituted or unsubstituted C6-C10 aryl groups.
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Page/Page column 10; 11
(2015/01/06)
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- ROSUVASTATIN CALCIUM INTERMEDIATE AND PREPARATION METHOD THEREOF
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A rosuvastatin calcium intermediate as shown by Formula I is prepared as follow: a) subjecting chloroethylene, magnesium and R-epoxy chloropropane to Grignard reaction, b) adding sodium cyanide for nucleophilic substitution reaction, c) adding alcohol for alcoholysis reaction, d) adding alkaline solvent for hydroxyl protection, e) subjecting the mixture to oxidation reaction, f) adding triphenyl phosphorus and subjecting to Wittig reaction in the presence of alkali to obtain the compound of formula I. The method has moderate reaction conditions, is convenient and stable and can be applied to industrial production.
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Paragraph 0056; 0057; 0058; 0059
(2013/03/26)
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- ROSUVASTATIN CALCIUM INTERMEDIATE AND METHOD FOR PREPARING THE SAME
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A method for preparing a rosuvastatin calcium intermediate, including a) contacting a halogenated ethene with magnesium metal to obtain a halogenated ethene Grignard reagent, and carrying out a Grignard reaction between the halogenated ethene Grignard reagent and R-epichlorohydrin; b) adding sodium cyanide for carrying out a nucleophilic substitution reaction; c) adding alcohol for carrying out an alcoholysis reaction; d) adding a basic solvent for carrying out protection of a first hydroxyl group; e) selectively oxidizing a second hydroxyl group; and f) adding triphenylphosphine in alkaline condition for carrying out a Wittig reaction.
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Page/Page column 5
(2012/12/14)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF AN INTERMEDIATE OF HMG-COA REDUCTASE INHIBITORS
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The present invention relates to an improved process for the preparation of intermediates of HMG-CoA reductase inhibitors of Formulae-IXa or IXb and further conversion to HMG-CoA reductase inhibitors and pharmaceutically acceptable salts thereof.
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- A PROCESS FOR THE PREPARATION OF ROSUVASTATIN INVOLVING A TEMPO-MEDIATED OXIDATION STEP
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The present invention provides a process for the preparation of the rosuvastatin intermediate FPP-CHO and its conversion to rosuvastatin and pharmaceutically acceptable salts thereof.
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Page/Page column 14
(2010/10/20)
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- Optically active intermediate and method for production thereof
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The present invention relates to a synthetic method of optically active starting materials for various medicaments, which are represented by Formula (I): STR1 wherein R1 is hydrogen or hydroxy protecting group; * is an asymmetric carbon; R2 ' is hydrogen or an optionally substituted lower alkyl; and Q is --CH=P(Ph)3, --CH2 P(O)(OMe)2, or --CH2 S(O)Me, in high optical purity on a large scale. In more detail, the present invention provides intermediates and a method for the production thereof for synthesizing optically active compounds which are able to inhibit activities of HMG-CoA reductase and are, therefore, useful for inhibition of cholesterol biosynthesis.
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- Practical synthesis of chiral synthons for the preparation of HMG-CoA reductase inhibitors
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A practical procedure for the enantioselective preparation of optically pure (R)- and (S)-monomethyl esters of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic acid has been developed by diastereoselective ring-opening of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic anhydride 5 by benzyl (R)- and (S)-mandelate, respectively. These half-esters afforded chiral Wittig reagent 2 and Horner-Wadsworth-Emmons (HWE) reagent 1 efficiently which have been proved to be useful in the synthesis of HMG-CoA reductase inhibitors. The method is applied to the synthesis of the (R)-3-methylglutaric acid, monomethyl ester.
- Konoike,Araki
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p. 7849 - 7854
(2007/10/02)
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- PYRIMIDINE DERIVATIVES
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The compounds of the present invention inhibit the HMG-CoA reductase, and subsequently suppress the biosynthesis of cholesterol. And they are useful in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis
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