Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for preparing tetraene acetate

A technology of tetraene acetate and tetraene, applied in the direction of steroids, organic chemistry, etc., can solve the problems of unsuitable industrial production, combustion and explosion accidents, etc., and achieve the effect of simple operation, less corrosion of equipment, and great application value

Active Publication Date: 2018-11-30
YANGZHOU LIANAO BIOMEDICAL CO LTD
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in industrial production, it is a very dangerous operation to introduce oxygen into an organic flammable solvent, which means that the three elements of combustion already have combustibles and combustion-supporting substances. If static electricity is generated, combustion and explosion accidents may occur. This reaction is also typical. One of the key regulatory hazardous chemical processes
Simultaneously, the chloride ion and copper ion that palladium chloride and cupric chloride contain are very strong to stainless steel reactor and metal piping corrosion, are not suitable for industrialized production, for this reason, research and development are suitable for the acetic acid of industrialized production The method of tetraene is especially important

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
  • Method for preparing tetraene acetate
  • Method for preparing tetraene acetate
  • Method for preparing tetraene acetate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022]

[0023] Add 35.0g (0.10mol, 1.0equiv ), 11.9g (0.11mol, 1.1equiv) of p-benzoquinone, 0.45g (0.002mol, 0.02equiv) of palladium acetate, add 500mL of methanol as a solvent, replace with nitrogen and heat to 30°C for 6 hours to generate intermediate 18-hydroxy Pregna-1,4,9(11),17-tetraene-3,19-dione-18-acetate. After the reaction is finished, distill under reduced pressure (distillation temperature is 30°C, vacuum degree is -0.08MPa) to remove the solvent, add 500mL ethyl acetate and stir to dissolve, add 300mL 5% disodium ethylenediaminetetraacetate (disodium EDTA) respectively Aqueous solution, 300mL 5% sodium bisulfite aqueous solution and 300mL water were washed once, the organic layer was dried with anhydrous sodium sulfate and then heated to 50°C, DBU3.0g (0.02mol, 0.2equiv) was added under the protection of nitrogen, and the reaction was kept for 5 hours Cool down to room temperature at 25°C, slowly add glacial acetic acid dropwise to adjust the pH to 6, add 30...

Embodiment 2

[0025]

[0026] Add 35.0g (0.10mol, 1.0equiv ), p-benzoquinone 10.8g (0.10mol, 1.0equiv), palladium acetate 0.11 (0.0005mol, 0.005equiv), add dimethyl sulfoxide 500mL as a solvent, replace with nitrogen and heat to 60°C for 6 hours to generate an intermediate 18-Hydroxypregna-1,4,9(11),17-tetraene-3,19-dione-18-acetate. After the reaction is over, remove most of the solvent by distillation under reduced pressure (distillation temperature is 75°C, vacuum degree is about -0.06MPa), add 500mL ethyl acetate and stir to dissolve, add 300mL 5% disodium ethylenediaminetetraacetic acid (EDTA Disodium) aqueous solution, 300mL 5% sodium bisulfite aqueous solution and 300mL water were washed once, the organic layer was dried with anhydrous sodium sulfate and then heated to 50°C, and DBU 3.0g (0.02mol, 0.2equiv) was added under nitrogen protection, and the reaction was kept After 5 hours, it was lowered to room temperature at 25°C, slowly added dropwise glacial acetic acid to adjust t...

Embodiment 3

[0028]

[0029] Add 35.0g (0.10mol, 1.0equiv ), p-benzoquinone 21.6g (0.20mol, 2.0equiv), palladium acetate 2.24g (0.01mol, 0.1equiv), add 500mL of dichloromethane as a solvent, replace with nitrogen, cool to 0°C and react for 6 hours to generate intermediate 18 -Hydroxypregna-1,4,9(11),17-tetraene-3,19-dione-18-acetate. After the reaction was finished, all solvents were removed by distillation under normal pressure, 500 mL of ethyl acetate was added and stirred to dissolve, and 300 mL of 5% ethylenediaminetetraacetic acid disodium (disodium EDTA) aqueous solution, 300 mL of 5% sodium bisulfite aqueous solution and 300 mL of water were added respectively. Wash once, dry the organic layer with anhydrous sodium sulfate, then heat up to 50°C, add DBU3.0g (0.02mol, 0.2equiv) under nitrogen protection, keep warm for 5 hours, then cool down to room temperature 25°C, slowly add glacial acetic acid dropwise to adjust the pH To 6, add 300mL of water to wash once, and the organic la...

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 method for preparing tetraene acetate. The method comprises the steps of subjecting a raw material, i.e., 17-ynepregna-1,4,9(11)-trien-3-one-17-hydroxyl acetate to a reactionin an organic solvent in the presence of a catalyst, i.e., palladium acetate and an oxidant, i.e., p-benzoquinone under the protection of inert gas so as to produce an intermediate, i.e., 18-hydroxylpregna-1,4,9(11),17-tetraen-3,19-dion-18-acetate, and carrying out treatment by using 1,8-diazabicycloundec-7-ene, thereby obtaining the tetraene acetate (21-hydroxylpregna-1,4,9(11),16-tetraen-3,20-dion-21-acetate)According to the method provided by the invention, the use of palladium chloride, copper chloride and oxygen is avoided, the corrosion to equipment is low, and meanwhile, the purity of the product is improved. The method has the advantages of being safe and efficient, being simple and convenient in operation, being satisfactory for industrial production, and the like and has a relatively high application value.

Description

technical field [0001] The invention relates to the preparation of medicines, in particular to a preparation method of a medicine intermediate, in particular to a preparation method of tetraenyl acetate. Background technique [0002] Tetraenyl acetate (21-hydroxypregna-1,4,9(11), 16-tetraene-3,20-dione-21-acetate, 3TR) is a synthetic triamcinolone acetonide, dexamethasone, budes It is an important intermediate of steroidal drugs such as Ned, and has a large market demand. The structure of tetraenyl acetate is as follows: [0003] [0004] Chinese patent CN102603843 reports a preparation method of tetraenyl acetate, using potassium tetrabromopalladate or palladium chloride as a catalyst, copper chloride as a cocatalyst, oxygen or air as an oxidant, and realizing the intermediate of the key acetylenide in an organic solvent Oxidation of the body to an aldehyde produces 18-hydroxypregna-1,4,9(11),17-tetraene-3,19-dione-18-acetate. However, in industrial production, it is ...

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): C07J7/00
CPCC07J7/008
Inventor 谢晓强徐雅峰张德法张毅
Owner YANGZHOU LIANAO BIOMEDICAL CO LTD