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

Tricyclic acetate compound with optical activity, and preparation method and application thereof

An optically active compound technology, applied to optically active tricyclic acetate compounds, the application of ramelteon and its optical isomers, the field of salts formed by optically active 2-acetic acid and chiral amines , which can solve the problems of excessive heavy metals in the product, high preparation cost of ramelteon, and low total yield.

Inactive Publication Date: 2012-08-01
SICHUAN UNIV
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] The above-mentioned method for synthesizing optically active ramelteon has higher raw material prices and is not easy to obtain (such as: [RuCl(benzene) (R)- BINAP]Cl, Ru(OAc) 2 -[ (R) -BINAP], Ru 2 Cl 4 [ (R) -BINAP] 2 NET 3 , amidohydrolase, etc.); the reaction conditions are harsh (requires absolute anhydrous solvent, high-pressure hydrogenation); there are many reaction steps and the total yield is low; the "three wastes" are seriously discharged during the preparation process; Insufficiencies such as excessive heavy metals make the preparation cost of ramelteon higher, and the large-scale preparation is limited

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
  • Tricyclic acetate compound with optical activity, and preparation method and application thereof
  • Tricyclic acetate compound with optical activity, and preparation method and application thereof
  • Tricyclic acetate compound with optical activity, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] (1,6,7,8-tetrahydro-2 H Preparation of -indeno-[5,4-b]furan-8-ylidene)acetonitrile (2)

[0065] Add 21.27 g (0.12 mol) of diethyl cyanomethylene phosphonate, 1,2,6,7-tetrahydro-8 H -Indeno-[5,4-b]furan-8-one 17.42 g (0.10 mol), toluene 120 ml and deionized water 60 ml, after stirring at room temperature, add tetrabutylammonium bromide 1.62 g (0.005 mol ) and 20.70 g (0.15 mol) of anhydrous potassium carbonate, heat up to 60-70°C, heat and stir for 8 h; after the reaction, cool to room temperature, separate the toluene layer, extract the water layer with 30 ml toluene, and combine the toluene solution , washed with 25 ml of saturated NaCl aqueous solution, the solvent was evaporated under reduced pressure, and the residue was recrystallized from methanol to obtain 17.20 g of light yellow crystalline solid, mp: 146~148°C, yield 87.2%.

Embodiment 2

[0067] (1,6,7,8-tetrahydro-2 H Preparation of -indeno-[5,4-b]furan-8-ylidene)acetonitrile (2)

[0068] Add 40.54 g (0.12 mol) of cyanomethylenetriphenylphosphonium chloride, 1,2,6,7-tetrahydro-8 H -Indeno-[5,4-b]furan-8-one 17.42 g (0.10 mol) and toluene 200 ml, after stirring at room temperature, cool to 0-5°C in an ice bath, add 15% sodium methoxide dropwise Methanol solution (0.13 mol), after dropping, remove the ice bath, stir at room temperature for 2.5 h, add 100 ml of deionized water into the reaction bottle, stir for 30 min, pour the reaction solution into a separatory funnel, separate the organic layer, And washed with 40 ml of saturated NaCl aqueous solution, the solvent was evaporated under reduced pressure, and the residue was recrystallized from methanol to obtain 16.51 g of light yellow crystalline solid, mp: 145~148 °C, yield 83.7%.

Embodiment 3

[0070] (1,6,7,8-tetrahydro-2 H Preparation of -indeno-[5,4-b]furan-8-ylidene)methyl acetate (3a)

[0071] The operation process is the same as in Example 1, except that diethyl cyanomethylene phosphonate is replaced with 2-(diethoxyphosphonic acid) methyl acetate to obtain (1,6,7,8-tetrahydro-2 H -indeno-[5,4-b]furan-8-ylidene)methyl acetate as light yellow oily liquid, yield 92.1%. It was directly used in the next reaction without further purification.

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 belongs to the field of medicinal chemistry, and relates to salt formed by 2-(1,6,7,8-tetralin-2H-indeno-[5,4-b]furan-8-yl) acetic acid with optical activity and chiral amine, a preparation method for the salt and application of the salt to the preparation of ramelteon for treating insomnia and an optical isomer of the ramelteon.

Description

[0001] related application [0002] This application is a divisional application, the application number of the original application is 200810045870.5, the application date is August 22, 2008, and the name of the invention is "compounds for preparing ramelteon, its preparation method and application". [0003] technical field [0004] The invention belongs to the field of medicinal chemistry and relates to optically active tricyclic acetate compounds, in particular to optically active 2-(1,6,7,8-tetrahydro-2 H -Indeno-[5,4-b]furan-8-yl)acetic acid and chiral amine salt, its preparation method and in the preparation of insomnia treatment drug - Ramelteon (Ramelteon) and its optical isomerism application in the body. [0005] Background technique [0006] The chemical name of ramelteon is: (S) - N -[2-(1,6,7,8-tetrahydro-2 H -Indeno-[5,4-b]furan-8-yl)ethyl]propionamide is a potent and highly selective melatonin receptor agonist that binds to the suprachiasmatic nucleus (...

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): C07D307/77
Inventor 邓勇李梅沈怡钟裕国
Owner SICHUAN UNIV
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