Check patentability & draft patents in minutes with Patsnap Eureka AI!

Process and intermediates for the selective synthesis of fluvastatin and use thereof

A kind of use, selected technology, applied in the intermediate compound of synthetic fluvastatin drug and its preparation, selective preparation of fluvastatin sodium field, can solve low concentration, difficulty in separation of stereoisomers, increased solvent consumption, etc. question

Inactive Publication Date: 2006-03-01
ZHEJIANG HISUN PHARMA CO LTD
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] A particular problem in the preparation of compound I is the formation of the 3,5-dihydroxyl side chain, which requires the formation of the cis stereoisomer, i.e. the formation of the 3R,5S / 3S,5R-enantiomer, the undesired reaction Formula isomers are only allowed in very small concentrations
[0007] Separation of stereoisomers is also very difficult due to the large volumes handled in large-scale industrial production
Recrystallization and chromatographic separation will increase solvent consumption, which is not only uneconomical, but also ecologically unreasonable

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Process and intermediates for the selective synthesis of fluvastatin and use thereof
  • Process and intermediates for the selective synthesis of fluvastatin and use thereof
  • Process and intermediates for the selective synthesis of fluvastatin and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1: 3-tert-butyldimethylsilyloxy-1,5-glutaric acid monomethyl ester (S-2-TBS)

[0054]

[0055] Under the protection of nitrogen, 18kg of 3-tert-butyldimethylsilyloxy-1,5-glutaric anhydride (S1) was dissolved in 90L of anhydrous methanol, heated to reflux for 24 hours, checked by TLC, and concentrated to Dry to obtain 20.0 kg of monomethyl ester.

Embodiment 2

[0056] Example 2: 3-tert-butyldimethylsilyloxy-6,6-dimethoxyphosphino-5-oxo-hexanoic acid (S-3-TBS)

[0057]

[0058] Under nitrogen protection, at -78°C, add 168.6L of n-butyllithium / ethyl ether dropwise to 35.9kg of dimethyl methyl phosphate / THF solution within 15 minutes, after the addition, stir and react at -78°C for 30 minutes . Then 20.0kg of S-2-TBS / THF solution was added dropwise within 5 minutes, stirred and kept at -78°C for 3 hours, then saturated ammonium chloride solution was added dropwise to stop the reaction, acidified with 2N hydrochloric acid, extracted with ethyl acetate, The layers were separated, the aqueous layer was stripped once with ethyl acetate, the combined organic layers were washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to obtain 27.6 kg of S-3-TBS.

Embodiment 3

[0059] Example 3: 3-tert-butyldimethylsilyloxy-6,6-dimethoxyphosphino-5-oxo-hexanoic acid methyl ester (IV-TBS)

[0060]

[0061] Dissolve 27.6kg of S-3-TBS in 220L of acetone, then add 53.3kg of iodomethane and 10.4kg of potassium carbonate in sequence, stir at room temperature for 24 hours (TLC inspection), and add water to terminate the reaction. Extract twice with ethyl acetate, combine the organic layers, wash once with saturated brine, dry over anhydrous sodium sulfate, and concentrate to dryness to obtain 24.7kg of IV-TBS.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a process and intermediates for the selective synthesis of fluvastatin and use thereof. The invention obtains an improtant intermediates of fluvastatin compound III prepared by the reaction of a compound of formula F1 and a compound of formula IV, and a syn-(E)-fluvastatin photoactive isomer through the selective synthesis from the compound of formula III. The invention also relates to a process and use for preparing the syn-(E)-fluvastatin photoactive isomer using the compound of formula III. The syn-(E)-fluvastatin photoactive isomer prepared by the inventive method has a high purity, the product of which can not have a three-dimensional isomer separation, that is, the isomer can be used as activated pharmaceutical compositions .

Description

technical field [0001] The invention relates to the fields of organic chemistry and medicinal chemistry, in particular, the invention relates to an intermediate compound for synthesizing fluvastatin (Fluvastatin) medicine and its preparation method and application. The present invention relates to the selective synthesis of cis-(E)-7-[3-(4-fluorophenyl)-1-isopropyl-2-indole]-3,5-dihydroxy-6-heptanoic acid (fluoro Vastatin, I) and new synthetic intermediates and new synthetic methods of pharmaceutically acceptable esters and salts. In particular, the present invention relates to a method for the selective preparation of fluvastatin sodium (I-Na) for lowering total cholesterol levels as well as low density lipoprotein levels in plasma. [0002] Background technique [0003] A particular problem in the preparation of compound I is the formation of the 3,5-dihydroxyl side chain, which requires the formation of the cis stereoisomer, i.e. the formation of the 3R,5S / 3S,5R-enant...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D209/12C07F9/40
CPCC07F9/4006C07D209/24
Inventor 朱国荣斯蒂芬・贝克尔
Owner ZHEJIANG HISUN PHARMA CO LTD
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com