Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for preparing heptenoic acid cyclopentyl ester derivative

A technology of cyclopentyl heptenoate and its derivatives, which is applied in the field of preparation of cyclopentyl heptenoate derivatives, can solve the problems of unfavorable high-quality products and poor effects, and achieve high overall yield of the route and increase Safety, effect of short synthesis steps

Inactive Publication Date: 2017-03-08
NANTONG CHANGYOO PHARMATECH CO LTD
View PDF9 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This route is an improved route of the basic patent route. Although it is purified by conversion into methylamine salt, the effect is not good, which is not conducive to the production of high-quality products

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
  • Method for preparing heptenoic acid cyclopentyl ester derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Synthesis of Intermediate I:

[0033] Add 500mL methanol and 30g (4R-cis)-6-[(acetoxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester into the reaction flask and 27.8g of potassium carbonate, stirred and dissolved, reacted at 20-25°C, and monitored the reaction by TLC. After the reaction is over, add 10mL of glacial acetic acid to the reaction solution, stir, heat up to 45-50°C and distill methanol off under reduced pressure, then add 300mL of toluene and 200mL of water, stir, and let stand to separate the liquids; the water layer is then extracted with 200mL of toluene, The organic phases were combined, dried over anhydrous sodium sulfate, filtered with suction, and the filtrate was concentrated to dryness under reduced pressure at 45-50°C to obtain 28.2 g of the product, which was directly subjected to the next reaction.

[0034] Synthesis of Intermediate II:

[0035] Add 28.2g of intermediate I and 300mL of methanol into the reaction flask, stir to ...

Embodiment 2

[0043] Synthesis of Intermediate I:

[0044] Add 700mL isopropanol, 45g (4R-cis)-6-[(acetoxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert- Butyl ester and 12.5g of sodium hydroxide were stirred and dissolved, reacted at 20-25°C, and monitored by TLC. After the reaction is over, add 20mL of glacial acetic acid to the reaction solution, stir, heat up to 45-50°C and distill off isopropanol under reduced pressure, then add 500mL of ethyl acetate and 300mL of water, stir, and let stand to separate the liquid; Extract with 500mL of ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, filter with suction, and concentrate the filtrate to dryness under reduced pressure at 45-50°C to obtain 42.3g of the product, which is directly subjected to the next reaction.

[0045] Synthesis of Intermediate II:

[0046] Add 42.3g of intermediate I and 300mL of isopropanol into the reaction flask, stir to dissolve, add 10.3g of lithium hydroxide, heat up to 45-50°C; k...

Embodiment 3

[0054] Synthesis of Intermediate I:

[0055] Add 700mL ethanol, 38g (4R-cis)-6-[(acetoxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester in the reaction flask and 6.4g of lithium hydroxide, stirred and dissolved, reacted at 20-25°C, and monitored the reaction by TLC. After the reaction is completed, add 15 mL of glacial acetic acid to the reaction solution, stir, heat up to 45-50 °C and distill off ethanol under reduced pressure, then add 450 mL of toluene and 250 mL of water, stir, and let stand to separate the liquids; the water layer is then extracted with 400 mL of toluene, The organic phases were combined, dried over anhydrous sodium sulfate, filtered with suction, and the filtrate was concentrated to dryness under reduced pressure at 45-50°C to obtain 35.9 g of the product, which was directly subjected to the next reaction.

[0056] Synthesis of Intermediate II:

[0057] Add 35.9g of intermediate I and 300mL of acetonitrile into the reaction flask, stir...

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 discloses a method for preparing a heptenoic acid cyclopentyl ester product by taking (4R-cis)-6-[(acetoxy)methyl]-2,2-dimethyl-1,3-dioxane-4-tert butyl acetate as an initial raw material, and the product is prepared through steps of hydrolysis, replacement and oxidation. The synthesis step is simple, an intermediate can be subjected to a next reaction without refining and purifying steps, for a butt-coupling reaction, the conventional mild technology condition can replace ultralow temperature reaction condition, superbase with high danger is simultaneously replaced, reaction security is increased, the route total yield is high, and the method is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a preparation method of a cyclopentyl heptenoate derivative, in particular to a preparation method of an important intermediate of rosuvastatin calcium. Background technique [0002] Rosuvastatin Calcium (Rosuvastatin Calcium) is the latest statin drug approved by AstraZeneca in Europe in 2002, and it is a "super statin" evaluated by the media. For the treatment of primary, familial hypercholesterolemia and mixed dyslipidemia. It was approved in the United States in August 2003, making it the seventh statin to hit the market. Its chemical name is: (3R,5S,6E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonamido)-5- Calcium pyrimidine]-3,5-dihydroxy-6-heptenoate. The structure is as formula 1: [0003] [0004] Patent EP0521471 first reported rosuvastatin calcium and its synthetic route. The route prepares ethylenic bond-containing compounds through Wittig reaction, and then obtains rosuvastatin calcium throu...

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): C07D239/42
CPCC07D239/42
Inventor 李泽标郭海峰王莹邹林严军马甜甜
Owner NANTONG CHANGYOO PHARMATECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com