cas 125995-13-3, (4R,6R)-tert-Butyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate

Articles about 125995-13-3Total 25 be found

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AN IMPROVED AND COMMERCIALLY VIABLE PROCESS FOR PREPARATION OF PYRROLE DERIVATIVES WITH IMPROVED IMPURITY PROFILE & MINIMISATION OF UNIT OPERATIONS.
The present invention relates to improved process for the preparation of a pyrrole derivative as a racemic mixture, an enantiomer, a diastereoisomer, a mixture thereof, a tautomer thereof or a pharmaceutically acceptable salt and hydrates thereof and also intermediates involved therein. Particularly invention is directed to improved processes for the preparation of pyrrole derivatives such as (4R,cis)-6-[2-[3-phenyl-4-(phenyl-carbamoyl)-2-(4-fluorophenyl)-5-(1-methyl-ethyl)-pyrrole-1-yl]-2,2-dimethyl-[1,3]dioxane-4-yl-acetic acid-tertiary butyl ester of formula IV followed by its conversion into [R-(R*, R*]-2-(4-fluorophenyl)- β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1- heptanoic acid particularly calcium salt and its hydrate represented by Formulae I/IA respectively wherein formation of the impurities is either eliminated or minimized in the corresponding intermediaries.
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Page/Page column 68; 69; 70-71

(2020/02/14)

Atorvastatin calcium intermediate as well as preparation method and application thereof
The invention discloses an atorvastatin calcium intermediate as well as a preparation method and application thereof. A synthesis process of the intermediate is environmentally-friendly, simple to operate and low in EHS risk; raw materials are easy to obtain; a used chemical reagent is small in toxicity and low in cost; and the synthesis process is a green synthesis process suitable for the industrial production. Moreover, the intermediate provided by the invention is applied to the synthesis of atorvastatin calcium and a key intermediate thereof, the route is relatively short, the yield is high, the industrial production cost of the atorvastatin calcium is effectively reduced, and the atorvastatin calcium intermediate has a relatively high industrial application prospect.
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(2019/04/04)

Preparation method of atorvastatin calcium intermediate
The invention belongs to the field of medicines and chemical industry, and particularly relates to the field of pharmacy, in particular to a preparation method of an atorvastatin calcium intermediate.The preparation method comprises the following steps: firstly preparing a compound II into a lithium reagent, then reacting with methyl chloroformate, introducing an ester group, aminolyzing the ester group into amine, dehydrating the amide, and finally reducing a cyano group to obtain a target compound. By the brand-new preparation method of the atorvastatin calcium intermediate, a compound VI can be synthesized under the premise that highly toxic substances such as hydrocyanic acid, hydrobromide and the like are not used, and the compound VI is used for preparing a compound I; reagents usedin the whole preparation process are safe and environment-friendly, and the preparation method is more suitable for industrial production.
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(2018/10/11)

A atorvastatin sandbank calcium chiral synthesis of intermediates method
The invention discloses a synthesis method for a chiral intermediate of atorvastatin calcium, and belongs to the technical field of medical intermediate synthesis. The synthesis method is characterized in that according to the process route, not only are dangerous, highly toxic and expensive chemicals such as butyl lithium, editpotassium cyanide and periodic acid in chemical synthesis prevented from being used, but also an ee value of the chiral intermediate is effectively improved due to usage of a mixed chiral catalysts of titanium iso-propylate and S-xenol. According to the synthesis method, the raw materials are low in cost and easy to obtain, the route operation is easy, the repeatability is good, the yield is very high, and the synthesis method is suitable for industrial production.
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(2017/08/24)

Preparation method of synthetic intermediate of Lipitor
The invention discloses a novel preparation method for a side-chain fragment compound, ATS-9, of Lipitor and solves a problem that poisonous reagents, such as Raney nickel, are required in synthesis in the prior art. The preparation method includes the steps of: with epoxy chloropropane as an initial raw material, performing a ring opening reaction with Grignard reagent to obtain a first chiral hydroxyl group; performing cyano substitution, hydrolyzing the substituted cyano group into ester, performing homologation reaction to extend the carbon chain, and performing reduction with diethylmethoxylborane and sodium borohydride, and protecting the two hydroxyl groups and finally performing the Staudinger reaction to prepare the ATS-9.
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(2016/10/09)

2 - ((4R, 6R) - 6-aminomethyl-ethyl -2,2-dimethyl -1,3-dioxane-4-yl) acetate simple method for preparing
The invention relates to a simple preparation method of 2-((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxyhexacyclo-4-yl)acetate (I). The method comprises the following steps: reacting 3-cyanopropylene (II) and 3,3-dialkoxypropionate (III) or 3-alkoxyacrylate (IV) under the catalytic action of Lewis acid to prepare 2-((4R,6R)-6-cyanomethyl-2-ester-methyl-1,3-dioxyhexacyclo-4-yl)acetate (V), removing the solvent, directly carrying out blocking group conversion to prepare 2-((4R,6R)-6-cyanomethyl-2,2-dimethyl-1,3-dioxyhexacyclo-4-yl)acetate (VI), and carrying out Raney nickel catalytic hydrogenation two-step reaction to prepare (I). The stable form of the hexatomic ring chair-structure equatorial bond is utilized to construct the chiral center without using any additional chiral assistant. The method has the advantages of accessible raw materials, short reaction procedure and low cost, avoids carbonyl asymmetric reduction, is simple and environment-friendly, and is industrial production.
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Paragraph 0066-0067

(2017/02/28)

Photochemical Formation and Cleavage of C-N Bond
A new photochemical method of C-N bond formation has been developed. A properly substituted trityl alcohol can cleave the benzylic C-O bond and replace it with a C-N bond which is stable under the irradiation conditions. The C-N bond can then be photochemically cleaved with the same light source when the nitrogen is protonated. (Chemical Presented).
Wang, Pengfei,Lu, Wenya,Devalankar, Dattatray,Ding, Zhenying
supporting information
p. 170 - 172
(2015/07/28)

THIOAMIDE COMPOUND, METHOD FOR PRODUCING THIOAMIDE COMPOUND, METHOD FOR PRODUCING [(4R,6R)-6-AMINOETHYL-1,3-DIOXANE-4-YL]ACETATE DERIVATIVE, AND METHOD FOR PRODUCING ATORVASTATIN
A thioamide compound represented by the following general formula (1): wherein, in the general formula (1), R1 represents one of -OR11 and -NR12R13; R2 and R3 each independently represent one of a protecting group of an amide group and a hydrogen atom; the R11 represents one of a protecting group of a hydroxyl group and a hydrogen atom; and the R12 and R13 each independently represent one of a protecting group of an amino group and a hydrogen atom, where the R12 and R13 may together form a protecting group having a cyclic structure.
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Paragraph 0161

(2014/01/17)

An improved process for chiron synthesis of the atorvastatin side chain
An improved and practical synthesis of tert-butyl ((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetate 3 has been developed for supplying this key chiral side-chain of atorvastatin by using a Blaise reaction of (S)-4-chloro-3-((trimethylsilyl)oxy)butanenitrile 7 and the Raney Ni catalyzed hydrogenation of tert-butyl 2-((4R,6R)-6-(-2-oximeethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate 12 as the key steps. This nine-step route from (R)-epichlorohydrin afforded the target compound in 55% overall yield of high chemical and enantiomeric purity.
Xiong, Fang-Jun,Li, Jie,Chen, Xiao-Fei,Chen, Wen-Xue,Chen, Fen-Er
p. 1205 - 1208
(2015/03/03)

Microencapsulated catalyst
The present invention relates to a catalyst system. In particular the invention relates to a catalyst in the form of metal or an alloy that is encapsulated within a polymer shell or matrix. More specifically the invention is directed towards reactive catalytic metals that may be pyrophoric or otherwise reactive in air and/or susceptible to oxidation. In particular, the invention is concerned with catalysts based on nickel.
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Page/Page column 18; 19

(2013/11/05)

Spectroscopic characterization and quantitative determination of atorvastatin calcium impurities by novel HPLC method
Seven process related impurities were identified by LC-MS in the atorvastatin calcium drug substance. These impurities were identified by LC-MS. The structure of impurities was confirmed by modern spectroscopic techniques like 1H NMR and IR and physicochemical studies conducted by using synthesized authentic reference compounds. The synthesized reference samples of the impurity compounds were used for the quantitative HPLC determination. These impurities were detected by newly developed gradient, reverse phase high performance liquid chromatographic (HPLC) method. The system suitability of HPLC analysis established the validity of the separation. The analytical method was validated according to International Conference of Harmonization (ICH) with respect to specificity, precision, accuracy, linearity, robustness and stability of analytical solutions to demonstrate the power of newly developed HPLC method.
Gupta, Lokesh Kumar
p. 495 - 501,7
(2012/12/11)

Spectroscopic characterization and quantitative determination of atorvastatin calcium impurities by novel HPLC method
Seven process related impurities were identified by LC-MS in the atorvastatin calcium drug substance. These impurities were identified by LC-MS. The structure of impurities was confirmed by modern spectroscopic techniques like 1H NMR and IR and physicochemical studies conducted by using synthesized authentic reference compounds. The synthesized reference samples of the impurity compounds were used for the quantitative HPLC determination. These impurities were detected by newly developed gradient, reverse phase high performance liquid chromatographic (HPLC) method. The system suitability of HPLC analysis established the validity of the separation. The analytical method was validated according to International Conference of Harmonization (ICH) with respect to specificity, precision, accuracy, linearity, robustness and stability of analytical solutions to demonstrate the power of newly developed HPLC method.
Gupta, Lokesh Kumar
p. 495 - 501
(2013/01/13)

A simplified catalytic system for direct catalytic asymmetric aldol reaction of thioamides; Application to an enantioselective synthesis of atorvastatin
A new catalytic system was developed for the direct catalytic asymmetric aldol reaction of thioamides. The new lithium-free Cu catalyst (second-generation catalyst) exhibited enhanced catalytic efficiency over the previously developed catalyst comprising [Cu(CH3CN) 4]PF6/Ph-BPE/LiOAr (first-generation catalyst), which required a tedious catalyst preparation process. In the reaction with the second-generation catalyst, the intermediate Cu-aldolate functioned as a Bronsted base to generate thioamide enolate, efficiently driving the catalytic cycle. The present aldol methodology culminated in a concise asymmetric synthesis of atorvastatin (Lipitor: atorvastatin calcium), a widely prescribed HMG-CoA reductase inhibitor for lowering low-density lipoprotein cholesterol.
Kawato, Yuji,Iwata, Mitsutaka,Yazaki, Ryo,Kumagai, Naoya,Shibasaki, Masakatsu
p. 6539 - 6546
(2011/09/20)

PROCESS FOR THE PRODUCTION OF ATORVASTATIN CALCIUM IN AMORPHOUS FORM
A process for the production of amorphous atorvastatin calcium and stabilized, amorphous atorvastatin calcium is provided.
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Page/Page column 11

(2009/09/07)

PROCESS FOR THE PREPARATION OF ATORVASTATIN CALCIUM
The present invention relates to process for the preparation of atorvastatin calcium. The process provides the novel approach for the synthesis of an important intermediate atorvastatin protected diol chemically (4R-cis)-6-[-2-[3-phenyl-4-(phenyl- carbamoyl)-2-(4-flourophenyl)-5-(1-methyl-ethyl)-pyrrol-1-yl]-ethyl]-2,2-dimethyl- [1,3]dioxane-4-yl-acetic acid-tertriay butyl ester for atorvastatin calcium i.e. [R- (R*,R*)]-2-(4-fluorophenyl-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4- [(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1). The present invention relates the use of amino side chain i.e [6-(2-aminoethyl)-2,2,-dimethyl- [1,3]dioxan-4-yl]-acetic acid tert-butyl ester and stetter compound i.e. 4-(4- Fluoroρhenyl)-2-isobutryl-4-oxo-N-phenyl butryl amide as an important starting materials for the preparation of atorvastatin protected diol in the high yield and thereby the recovery of amino side chain with an industrially applicable process.
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Page/Page column 7

(2008/06/13)

CRYSTAL FORM OF SODIUM; (3R,5R)-7-[4-BENZYLCARBAMOYL-2-(4-FLUOROPHENYL)-5-ISOPROPYL-IMIDAZOL-1-YL]-3,5-DIHYDROXY-HEPTANOATE
A crystal form A of sodium; (3R, 5R)-7-[4-benzylcarbamoyl-2-(4-fluoropheynl)-5-isopropyl- imidazol-1-yl]-3,5-dihydroxy-heptanoate is provided.
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Page/Page column 17-18

(2010/11/27)

PREPARATION OF AN ATORVASTATIN INTERMEDIATE
Atorvastatin lactone is prepared by hydrogenating tert-butyl isopropylidene nitrile to tert-butyl isopropylidene amine and condensing the amine with the diketone of atorvastatin to form acetonide ester. The diol protecting acetonide ester is deprotected to form a diol ester by dissolving the acetonide ester in methanol and treating with an acid. The diol ester is saponified to form a sodium salt. Methanol is removed from the reaction mixture by distillation. The sodium salt is reacidified to the free diol acid and atorvastatin lactone is formed from the diol acid. The atorvastatin lactone is directly dried without further purification.
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Page/Page column 6-9; 11

(2008/06/13)

AMORPHOUS ATORVASTATIN CALCIUM
Amorphous atorvastatin calcium having an enhanced stability contains about 2 to about 8 percent by weight water. A process for preparing the amorphous atorvastatin calcium and a packaging system for maintaining the stability are described.
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Page/Page column 8; 2/2

(2008/06/13)

Process for the production of atorvastatin calcium un amorphous form
A process for the production of amorphous atorvastatin calcium and stabilized, amorphous atorvastatin calcium is provided.
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Page/Page column 3; 17

(2010/11/30)

Novel imidazoles
Novel imidazoles are provided. The compounds are useful as HMGCo-A Reductase Inhibitor. Also provided are pharmaceutical compositions of the compounds. Methods of making and methods of using the compounds are also provided.
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Page/Page column 83

(2010/02/14)

Process for the production of atorvastatin calcium in amorphous form
A process for the production of amorphous atorvastatin calcium and stabilized, amorphous atorvastatin calcium is provided.
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Page/Page column 5; 9

(2010/02/14)

CRYSTALLINE FORM OF ATORVASTATIN HEMI CALCIUM
The present invention relates to novel crystalline form R of atorvastatin hemi calcium salt and hydrates thereof useful as pharmaceutical agents, to methods for their production and isolation, to pharmaceutical compositions which include novel crystalline form R of atorvastatin hemi calcium salt and hydrates thereof and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment.
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Page/Page column 13

(2010/02/14)

Sequential aldol condensation catalyzed by DERA mutant Ser238Asp and a formal total synthesis of atorvastatin
A mutant D-2-deoxyribose-5-phosphate aldolase (DERA), Ser238Asp, was used to prepare β-hydroxy-δ-lactol synthons and a key intermediate for atorvastatin synthesis.
Liu, Junjie,Hsu, Che-Chang,Wong, Chi-Huey
p. 2439 - 2441
(2007/10/03)

A new way to tert-Butyl [(4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate, a key intermediate of atorvastatin synthesis
A new synthesis of tert-butyl [(4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate, a key intermediate of the synthesis of an effective HMG-CoA reductase inhibitor atorvastatin, is described. The synthesis is based on the Henry reaction of nitromethane and tert-butyl [(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl] acetate. The formed nitroaldol was then O-acetylated and the sodium borohydride reduction of the intermediate provided tert-butyl [(4R,6R)-2,2-dimethyl-6-nitroethyl-1,3-dioxan-4-yl] acetate. Catalytic hydrogenation of the nitro group led to the title compound.
Radl, Stanislav
p. 2275 - 2283
(2007/10/03)

The convergent synthesis of CI-981, an optically active, highly potent, tissue selective inhibitor of HMG-CoA reductase
The synthesis of CI-981 is described starting from isobutyrylacetanilide (3) and the key chiral intermediate 2.
Baumann,Butler,Deering,Mennen,Millar,Nanninga,Palmer,Roth
p. 2283 - 2284
(2007/10/02)