Preparation method of dezocine

A technology for dezocine and intermediates, which is applied in the field of preparation of dezocine, can solve the problems of low splitting efficiency and unsatisfactory splitting efficiency, and achieves cheap and easy-to-obtain reagents, mild reaction conditions, and simple and efficient process operation. Effect

Active Publication Date: 2012-06-20
JIANGSU HAICI BIOLOGICAL PHARMA CO LTD OF YANGTZE RIVER PHARMA GRP +1
View PDF1 Cites 33 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has the disadvantages of unsatisfactory splitting efficiency and low splitting efficiency

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
  • Preparation method of dezocine
  • Preparation method of dezocine
  • Preparation method of dezocine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Embodiment 1 prepares dezocine

[0043] The preparation method of the dezocine of the present embodiment comprises the following steps:

[0044] 1) Synthetic intermediate "Dezocine-1", raw material ratio:

[0045] raw material name

[0046] Reaction steps: under a nitrogen atmosphere, add magnesium chips (5kg, 210mol) and anhydrous ether (90L) into a dry reactor, use an ice-water bath to cool down, and slowly add bromomethane (23.5kg, 250mol) dropwise while stirring Diethyl ether (20L) solution, keep diethyl ether slightly reflux state. After dropping, heat to reflux and react for 1 hour to dissolve the magnesium bars completely. The starting material 7-methoxy-3,4-dihydro-1-naphthalenone (22.6kg, 130mol) in toluene (60L) was slowly dropped into the above-mentioned Grignard reagent under stirring, and the temperature was kept at 28 ~ 32°C, keep the original temperature after dropping and continue the reaction for 1h. Cool in an ice-salt bath, slowly add s...

Embodiment 2

[0077] Embodiment 2 prepares dezocine

[0078] The intermediate "Dezocine-1" was first synthesized according to the method in Example 1, and then the intermediate "Dezocine-2" was prepared from the intermediate "Dezocine-1" according to the following reaction steps.

[0079] The intermediate "Dezocine-1" (18.84kg, 110mol) was dissolved in chloroform (25L), and a solution of peroxyphenylacetic acid (20kg, 132mol) in chloroform (15L) was added dropwise at 0°C while stirring. After dropping, continue to stir for 4 hours at 0-5°C. After the reaction of the raw materials is monitored by TCL, 10% sodium hydroxide solution (30L) is added to the reactor, stirred for a while and left to separate liquids, and the organic phase is separated with 10% sodium hydroxide Wash with NaOH solution (2×10L), combine the aqueous phases and extract with chloroform (2×10L), combine the organic phases, wash with water (10L) once, and evaporate the solvent to obtain an oily substance. A mixture of 95%...

Embodiment 3

[0081] Embodiment 3 prepares dezocine

[0082] The intermediate "Dezocine-1" was first synthesized according to the method in Example 1, and then the intermediate "Dezocine-2" was prepared from the intermediate "Dezocine-1" according to the following reaction steps.

[0083] The intermediate "Dezocine-1" (18.84kg, 110mol) was dissolved in chloroform (25L), and a solution of peracetic acid (10kg, 132mol) in chloroform (15L) was added dropwise at 0°C while stirring. After dropping, continue to stir for 4 hours at 0-5°C. After the reaction of the raw materials is monitored by TCL, 10% sodium hydroxide solution (30L) is added to the reactor, stirred for a while and left to separate liquids, and the organic phase is separated with 10% sodium hydroxide Wash with NaOH solution (2×10L), combine the aqueous phases and extract with chloroform (2×10L), combine the organic phases, wash with water (10L) once, and evaporate the solvent to obtain an oily substance. A mixture of 95% ethanol ...

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 provides a preparation method of dezocine, which has the following advantages: (1) when an intermediate which is dezocine-1 is used as a raw material to prepare another intermediate which is dezocine-2, the obtained oxidants are acid peroxide, alcohol peroxide or hydrogen peroxide which have low cost and are easy to obtain and post-process; (2) when the intermediate which is dezocine-2 is used as a raw material to prepare an intermediate which is dezocine-3, the obtained bases are bases which have low cost and are easy to obtain; (3) when an intermediate which is dezocine-6 is used as a raw material to prepare an intermediate which is dezocine-6b, an optically pure chiral organic acid and an racemic intermediate which is the dezocine-6 react for generate a pair of diastereomeric salts, and then the pair of diastereomeric salts are separated through recrystallization to obtain the intermediate which is the dezocine-6 with high optical purity; and (4), the operation is simple and efficient, the reaction condition is mild, and the used reagents are cheap, readily available, highly safe and suitable for industrial mass production.

Description

technical field [0001] The invention relates to a preparation method of dezocine, which belongs to the technical field of medicinal chemistry. Background technique [0002] Dezocine, the scientific name is [5R-(5α, 11α, 13 S*)]-13-amino-5,6,7,8,9,10,11,12-octahydro-5-methyl-5 , 11-methylenebenzocyclodecene-3-ol, belongs to a typical opioid alkaloid analgesic drug, developed by Astra company in Sweden. These drugs work by stimulating opioid receptors. Dezocine has stronger analgesic effect than pentazocine, is a κ receptor agonist, and is also a μ receptor antagonist. Dezocine is less addictive and is suitable for the treatment of moderate to severe pain after surgery, visceral colic and pain in patients with advanced cancer. At present, dezocine has been approved for marketing by the State Administration of Drugs and Food of China, and has begun to be sold in China. Due to its good tolerance and safety, dezocine is expected to become an opioid alkaloid analgesic with goo...

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): C07C215/64C07C213/00
Inventor 朱其明路显峰冯建鹏韩成艳胡丽娜戚小燕徐凯靳涛
Owner JIANGSU HAICI BIOLOGICAL PHARMA CO LTD OF YANGTZE RIVER PHARMA GRP
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