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

Method for preparing landiolol intermediate

A technology for compounds and heterocycles, applied in the field of preparing methyl-3-[4-, can solve the problems of high cost of target products, difficult industrial production, expensive docking raw materials, etc., and achieves low cost, easy industrial production, and high purity. Effect

Inactive Publication Date: 2009-03-25
BEIJING D VENTUREPHARM TECH DEV
View PDF2 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The docking raw materials used in the above method are relatively expensive, and the post-processing method includes column chromatography, which leads to high cost of the target product, complicated operation, and difficulty in industrial production

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 landiolol intermediate
  • Method for preparing landiolol intermediate
  • Method for preparing landiolol intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Add 5g (2,2-dimethyl-1,3-dioxo-4S-heterocyclic)methyl-3-[4-hydroxyphenyl]propionate (compound of formula III) to a 100ml three-necked flask, 6.2 g of anhydrous potassium carbonate and 60ml of acetonitrile, stirred to dissolve. Heat to reflux. Under reflux conditions, 5g (R)-epichlorohydrin was added dropwise. After dropping, the mixture was refluxed for 14 hours, and the reaction was detected by TLC. After the reaction was completed, suction filtered, and the filtrate was concentrated under reduced pressure to obtain a pink oil. The oil was dissolved in ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate for 1 hour. Suction filtration, the filtrate was concentrated under reduced pressure to obtain 4.9g oily matter, i.e. (2,2-dimethyl-1,3-dioxo-4S-heterocyclic)methyl-3-[4-(2(S), 3-epoxypropyl)phenyl]propionate (compound of formula I), the yield is 90%. The purity is 97.5% (HPLC).

reference example 1

[0016] Reference Example 1 (Chem.Pharm.Bull.40(6)1462-1469(1992))

[0017] Add 1.23g (2,2-dimethyl-1,3-dioxo-4S-heterocycle)methyl-3-[4-hydroxyphenyl]propionate, 1.00g (2S) -(+)-Glycidyl tosylate, 1.21g of anhydrous potassium carbonate and 10ml of anhydrous N,N-dimethylformamide were stirred to dissolve. Heat to 70°C, and continue heating at 70°C for 15 hours. After the reaction was completed, 60 ml of ethyl acetate was added to the reaction solution, washed with distilled water and brine in turn, and the organic phase was dried over anhydrous magnesium sulfate. Suction filtration, the filtrate was concentrated under reduced pressure, and the oil was obtained for column chromatography (eluent: dichloromethane-ethyl acetate volume ratio 9:1) to obtain 1.18g of the target compound, namely (2,2-dimethyl- 1,3-Dioxy-4S-heterocycle)methyl-3-[4-(2(S),3-epoxypropyl)phenyl]propionate, the yield was 80%.

reference example 2

[0018] Reference example 2 (EP 0397031)

[0019] Add 950mg (2,2-dimethyl-1,3-dioxo-4S-heterocycle)methyl-3-[4-hydroxyphenyl]propionate, 0.58ml(R)- Epibromohydrin, 1.406g of anhydrous potassium carbonate and 15ml of acetone were stirred to dissolve. Heat to reflux. Reflux for 16 hours. TLC detection reaction. After the reaction was completed, suction filtered, and the filtrate was concentrated under reduced pressure to obtain an oil. The oil was dissolved in water and the organic phase was extracted with ethyl acetate. The organic phase was washed successively with distilled water and saturated brine, and dried over anhydrous magnesium sulfate. Suction filtration, the filtrate was concentrated under reduced pressure, and the oil was obtained for column chromatography (eluent: ethyl acetate-dichloromethane volume ratio 4:96), to obtain 869 mg of the target compound, namely (2,2-dimethyl-1 , 3-Dioxy-4S-heterocyclic)methyl-3-[4-(2(S),3-epoxypropyl)phenyl]propionate, the yiel...

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 method for preparing (2, 2-dimethyl-1, 3-dioxygen-4S-heterocycle) methyl-3-[4-(2(S), 3-glycidyl) phenyl] propionic ether (compound of formula I), which comprises the procedure of the reaction of the compound of formula III with epoxy chloropropane; and the compound is the key intermediate for preparing Landiolol.

Description

technical field [0001] The present invention relates to the preparation of (2,2-dimethyl-1,3-dioxo-4S-heterocyclic)methyl-3-[4-(2(S),3-epoxypropyl)phenyl]propane The method of acid ester, the compound is an important intermediate for the preparation of Landisolol. Background technique [0002] Landisolol has good pharmacological and therapeutic properties, so that the compound can be used to prevent and treat cardiovascular diseases. EP0397031 discloses Landisolol, a preparation method and a therapeutic application. [0003] [0004] EP0397031, JP5306281, Development of a Highly Cardioselective UltraShort-Acting β-Blocker, ONO-1101, Chem.Pharm.Bull.1992,40,1462-1469, report the method for preparing formula I compound, with acetone, toluene or N , N-dimethylformamide is a solvent, and the raw material used to dock with the compound of formula III is (2S)-(+)-glycidyl tosylate, (R)-epoxybromohydrin or (2S) -(+)-Glycidyl nitrobenzene sulfonate adopts the post-treatment pro...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D407/12
Inventor 薛绪飞
Owner BEIJING D VENTUREPHARM TECH DEV
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