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

N-demethylation of N-methyl morphinans

A methyl, alkoxycarbonyl technique applied in N-demethylation. field

Inactive Publication Date: 2010-11-24
MALLINCKRODT INC
View PDF1 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this method requires removal of the N-methyl substituent, which can produce a complex mixture of 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
  • N-demethylation of N-methyl morphinans
  • N-demethylation of N-methyl morphinans
  • N-demethylation of N-methyl morphinans

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0135] Example 1. Reaction of oripavine with ethyl chloroformate.

[0136] Oripavine and three different concentrations of ethyl chloroformate (ClCO 2 Et) reaction. Three samples of oripavine were prepared. For each, 0.3 g of oripavine was added to 5 mL of chloroform (CHCl 3 )middle. Once a solution is formed, the mixture is cooled to about 0-5°C. With stirring, 5 mL of saturated NaHCO 3 Add to each mixture. Different amounts of ClCO 2 Et, i.e., 1 equivalent, 2 equivalents or 3 equivalents of ClCO 2 Et (shown in Table 1) was added to each mixture. Each mixture was stirred at room temperature for 30 minutes after the addition of ethyl chloroformate, then sampled for HPLC to determine if the reaction was complete.

[0137] Table 1. Oripavine response.

[0138] sample#

[0139] As shown in Table 1, when oripavine and 3 equivalents of ClCO 2 The reaction was complete when Et (sample #3) reacted. For this sample, the organic solution was 5% NaHCO 3 (9 mL), 5%...

Embodiment 2

[0140] Embodiment 2. The reaction of thebaine and ethyl chloroformate.

[0141] To determine the correct ratio of thebaine and ethyl chloroformate, an experiment similar to Example 1 was carried out. For each sample, 0.31 g of thebaine was dissolved in 5 mL of CHCl 3 middle. Once a solution is formed, the mixture is cooled to about 0-5°C. With stirring, 5 mL of saturated NaHCO 3 Add to each mixture. ClCO 2 Et (as shown in Table 2) was added to each mixture, which was stirred at room temperature for 30 minutes, and then sampled for HPLC to determine whether the reaction was complete.

[0142] Table 2. Thebaine responses.

[0143] sample#

[0144] As shown in Table 2, when thebaine and 3 equivalents of ClCO 2 The reaction was complete when Et (sample #3) reacted. The sample was treated with 5% NaHCO as described above 3 , 5% HOAc and water washes. The organic layer was concentrated to dryness under partial vacuum to give 0.4 g of solid.

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
purityaaaaaaaaaa
Login to View More

Abstract

The present invention provides a synthetic process for the N-demethylation of N-methyl morphina'ns. In particular, the invention provides improved synthetic methods for the preparation of N-demethylated morphinan compounds that may be employed as starting materials, for example, commonly available N-methyl opiates such as oripavine and thebaine, and C (3) -protected hydroxy derivatives of oripavine.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to provisional application 61 / 014,086, filed December 17, 2007, which is hereby incorporated by reference in its entirety. technical field [0003] The present invention generally relates to the N-demethylation of N-methylmorphinans. Background technique [0004] Commercially valuable "nal" morphinan compounds or intermediates such as naltrexone, naloxone, nalbuphene, nalmefene and buprenorphine are generally unsubstituted from the heterocyclic nitrogen atom Preparation of normorphinan compounds. These normorphinan compounds may be derived from natural opiates or derivatives such as thebaine and oripavine. However, this method requires removal of the N-methyl substituent, which can result in a complex mixture of products. Therefore, there is a need for improved synthetic methods to prepare N-demethylated morphinan compounds. Contents of the invention [0005] Aspects of the presen...

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): C07D489/02
CPCC07D489/02A61P25/04
Inventor 彼得·X·王江涛加里·L·坎特雷尔戴维·W·伯布里克
Owner MALLINCKRODT INC
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