Synthetic method of naloxone hydrochloride

A technology of naloxone hydrochloride and naloxone, which is applied in the field of medicine, can solve problems such as low yield, environmental pollution, and serious injury to synthesis workers, and achieve the goals of low impurity content, excellent product quality, and increased reaction speed Effect

Active Publication Date: 2014-12-24
CHENGDU TIANTAISHAN PHARMA
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] The deficiency of this technology is that this technology is when compound generates compound 1, and reaction condition is not easy to control, easily takes place side reaction, and the yield of reaction is not high; This technology is in the production process from oxycodone to naloxone, always The yield is about 40%, and a large amount of toxic solvents such as chloroform and dichloroethane have been used in the previous production process, which will cause great harm to the synthesis staff and easily cause pollution to the environment

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
  • Synthetic method of naloxone hydrochloride
  • Synthetic method of naloxone hydrochloride
  • Synthetic method of naloxone hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Embodiment 1: Preparation of naloxone hydrochloride in dihydrate form

[0072] Step 1: Dissolve 10g of thebaine in 100ml of formic acid, keep warm at 20°C, stir and add 33g of m-chloroperoxybenzoic acid dropwise, after keeping warm for 5 hours, replace the system with nitrogen 4 times, add 0.5g of Raney nickel, and replace with hydrogen for 4 Once the system is stable, keep warm at 30°C, hydrogenate for 10 hours, filter, filter the cake (the filter cake is the catalyst), wash twice with 10ml of water, adjust the pH of the filtrate to 8-9 with 30% sodium hydroxide solution, filter, and vacuum the filter cake Dry to obtain compound 2, 8.12g;

[0073] Step 2: Add 8.12g of the compound obtained in the previous step into a reaction flask, add 82ml of acetic anhydride, heat up to 70°C, and react for 1 hour, then concentrate the system to dryness in vacuo to obtain Compound 3, 8.91g;

[0074] Step 3: Put 8.91g of the compound obtained in the previous step into the reaction f...

Embodiment 2

[0079] Embodiment 2: Preparation of naloxone hydrochloride in dihydrate form

[0080] Step 1: Dissolve 10g of thebaine in 110ml of formic acid, keep warm at 25°C, stir and add 35.2g of m-chloroperoxybenzoic acid dropwise, after keeping warm for 3 hours, replace the system with nitrogen for 5 times, add 0.6g of Raney nickel, and replace with hydrogen 4 times, wait for the system to be stable, keep warm at 25°C, hydrogenate for 12 hours, filter, filter cake (the filter cake is the catalyst), wash 2 times with 10ml water, adjust the pH of the filtrate to 8-9 with 30% sodium hydroxide solution, filter, and filter the cake Vacuum drying to obtain compound 2, 8.31g;

[0081] Step 2: Add 8.31 g of the compound obtained in the previous step into a reaction flask, add 84 ml of acetic anhydride, and raise the temperature to 60°C. After reacting for 1 hour, the system is concentrated to dryness in vacuo to obtain Compound 3, 8.78 g;

[0082] Step 3: Put 8.78g of the compound obtained ...

Embodiment 3

[0087] Embodiment 3: Preparation of naloxone hydrochloride in dihydrate form

[0088] Step 1: Dissolve 10g of thebaine in 130ml of formic acid, keep warm at 20°C, add 30g of m-chloroperoxybenzoic acid dropwise, keep warm for 7 hours, replace the system with nitrogen for 3 times, add 0.5g of Raney nickel, and replace with hydrogen for 5 times , when the system is stable, keep warm at 30°C, hydrogenate for 10 hours, filter, filter the cake (the filter cake is the catalyst), wash twice with 10ml of water, adjust the filtrate to PH=8-9 with 30% sodium hydroxide solution, filter, and dry the filter cake in vacuum Dry to obtain compound 2, 8.05g;

[0089] Step 2: Add 8.05 g of the compound obtained in the previous step into a reaction flask, add 92 ml of acetic anhydride, heat up to 80°C, and react for 1 hour, then concentrate the system to dryness in vacuo to obtain Compound 3, 8.73 g;

[0090] Step 3: Put 8.73g of the compound obtained in the previous step into a reaction flask...

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
specific rotationaaaaaaaaaa
Login to view more

Abstract

The invention belongs to the technical field of medicament synthesis, and relates to a synthetic method of naloxone hydrochloride. The method comprises the following steps: by adopting thebaine as a starting material, oxidizing and then reducing thebaine to obtain a compound 2, reacting the compound 2 with acetic anhydride to obtain an ester compound 3, then removing methyl and performing hydrolysis to obtain a compound 4, reacting the compound 4 with an alkylating reagent (such as the reagent selected from chloropropene, bromopropene, iodopropylene or the combination thereof), performing allylation on the Nth bit of a mother nucleus structure to obtain a compound 5, then removing methyl to obtain naloxone free alkali, then forming acid addition salts with hydrochloric acid, and then refining to obtain naloxone hydrochloride which can be used as a medicinal raw material medicament. By adopting the method disclosed by the invention, a high-quality medicinal raw material medicament can be prepared.

Description

technical field [0001] The invention belongs to the technical field of medicines, in particular to a naloxone hydrochloride compound, in particular to a synthesis method of the naloxone hydrochloride compound. Background technique [0002] Naloxone Hydrochloride, whose English name is Naloxone Hydrochloride, is the hydrochloride dihydrate of naloxone base, chemical name: 17-allyl-4,5α-epoxy-3,14-dihydroxymorphinan -6-one hydrochloride dihydrate, its chemical structure is: [0003] [0004] Naloxone hydrochloride is white crystal or crystalline powder, easily soluble in water, soluble in methanol, almost insoluble in chloroform or ether. [0005] Naloxone is a pure opioid receptor antagonist with no intrinsic activity itself. However, it can competitively antagonize various opioid receptors and has a strong affinity for μ receptors. Naloxone takes effect quickly and has a strong antagonistic effect. Naloxone also reverses all effects of opioid agonists, including analg...

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): C07D489/08
CPCC07D489/08
Inventor 方专王敬江威张莲莲余茹赵东明
Owner CHENGDU TIANTAISHAN PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap