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

Stereospecific method for the preparation of dioxa-bicyclooctane nitrate compounds

a dioxa-bicyclooctane nitrate and stereospecific technology, applied in the field of new stereospecific method for the preparation of dioxabicyclooctane nitrate compounds, can solve the problems of unsafe nitrating agents, unsatisfactory safety of acetic anhydride, and low yield of the preparation method, so as to achieve the effect of higher overall yield

Inactive Publication Date: 2011-10-13
LACER SA
View PDF0 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The method achieves higher yields exceeding 40% and eliminates the need for chromatographic purification, ensuring high purity and safer industrial-scale production of dioxa-bicyclooctane nitrate compounds.

Problems solved by technology

This preparation method affords less than 20% overall yield and involves chromatographic treatments after the thioacetylation step as well as after the nitration reaction.
In addition the nitration step involved the use of a mixture of nitric acid, acetic acid and acetic anhydride which is unsatisfactory from a safety point of view.
The need of chromatographic treatment and the use of unsafe nitrating agents are extremely disadvantageous for industrial-scale synthetic preparations.
Furthermore, both the low yield and the purification by chromatography are highly undesirable from an economic point of view.

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
  • Stereospecific method for the preparation of dioxa-bicyclooctane nitrate compounds
  • Stereospecific method for the preparation of dioxa-bicyclooctane nitrate compounds
  • Stereospecific method for the preparation of dioxa-bicyclooctane nitrate compounds

Examples

Experimental program
Comparison scheme
Effect test

example 1

Synthesis of 2-acetylthio-isosorbide 5-mononitrate

Step 1: Preparation of Isosorbide ditriflate

[0044]

[0045]Isosorbide (300 g), dichloromethane (7.5 L, 9.938 Kg) and pyridine (0.586 Kg) are charged to a 20 L flange flask. The resultant solution is cooled (3° C.) with stirring. Trifluoromethanesulfonic anhydride (0.749 L, 1.257 Kg) is added to the solution via dropping funnel.

[0046]The reaction is stirred out to room temperature for 1-2 hours and the reaction is quenched by the cautious addition of water (1.5 Kg).

[0047]The organic layer is removed and the aqueous layer is re-extracted with dichloromethane (0.750 L).

[0048]All organic layers are washed with 5M HCl acid solution and with water until neutral pH.

[0049]The organic layers are charged to 7.5 L of heptane, after that the dichloromethane was removed from the product mixture by distillation using partial vacuum such that vessel temperature does not exceed 50° C.

[0050]The resultant precipitate is cooled to 3° C. stirred for at lea...

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

PropertyMeasurementUnit
temperatureaaaaaaaaaa
solubilityaaaaaaaaaa
temperatureaaaaaaaaaa
Login to View More

Abstract

This invention relates to a new method for the stereospecific thiocarboxylation and nitration of organic compounds for the preparation of compounds according to formula (I):comprising the following steps:(a) reacting a compound of formula (II):with a sulfonic derivative of formula (III)wherein the R is selected from the groups C1-3-alkyl, C1-3-alkyl substituted with 1 to 3 halogen atoms, phenyl, C1-3-alkyl-phenyl and C1-3-alkyl-phenyl wherein the alkyl is substituted with 1 to 3 halogen atoms and G is a halogen atom or a group —O—SO2—R wherein R is as hereinabove definedto yield a compound of formula (IV)(b) treating compound (IV) with a thiocarboxylic acid of formula (V) or a salt thereof:wherein Z is as defined above, to yield compound (VI)and(c) treating compound (VI) with tetrabutylammonium nitrate to yield a compound of formula (I).

Description

FIELD OF THE INVENTION[0001]The present invention relates to a new stereospecific method for the preparation of dioxa-bicyclooctane nitrate compounds.BACKGROUND ART[0002]The nitric acid esters of organic compounds, commonly known as nitrated organic compounds, are known and have been used as vasodilating agents for some time. Among these, the usefulness of mono- and di-nitrated isosorbide is well known, and furthermore, compounds with vascular and coronary activities based on substitution reactions of the free hydroxyl group of isosorbide mononitrate have been described.[0003]Patent application WO 00 / 20420 describes isosorbide mononitrates wherein the free hydroxyl group is esterified with either carboxylic acids or with thioacids wherein said ester groups are in trans position with respect to the nitrate group.[0004]Patent application WO 2005 / 037842 describes isosorbide mononitrates wherein the free hydroxyl group has been replaced by a wide range of substituents.[0005]A particular...

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(United States)
IPC IPC(8): C07D493/04
CPCC07D493/04
Inventor REPOLLES MOLINER, JOSEPUBILL COY, FRANCISCOCABEZA LLORENTE, LYDIAMARTINEZ BONNIN, JOAN
Owner LACER SA
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