Preparation method of 19-nor-4-androstenedione

A technology of androstenedione and demethylation, which is applied in the field of preparation of pharmaceutical intermediates, can solve the problems of low product reaction yield, unsuitability for large-scale production, low yield of alkali dereaction, etc., and achieve high product purity, The effect of low cost and simple preparation process

Inactive Publication Date: 2010-10-06
上海津力药业股份有限公司
View PDF0 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] There are many kinds of preparation methods of 19-desmethyl-4-androstenedione in the prior art, mainly divided into two kinds of acid removal and alkali removal, wherein the method usually used is: androst-4-ene-19- Methanol-3,17-dione is oxidized with chromic anhydride-concentrated sulfuric acid to

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 19-nor-4-androstenedione
  • Preparation method of 19-nor-4-androstenedione
  • Preparation method of 19-nor-4-androstenedione

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0031] Example 1:

[0032] A preparation method of 19-desmethyl-4-androstenedione, the preparation process is mainly composed of three parts: addition reaction, decarboxylation oxide purification, and alkali dereaction. The specific preparation method and steps are as follows:

[0033] 1) Addition reaction: In a 100ml three-necked flask, add 56g of acetone, 4g of rearrangement, stir to dissolve, turn on the freezer, cool to -34℃, add 6g of drinking water, between -35--40℃, Add (trichloroisocyanuric acid 1.2g + acetone 8g) solution dropwise, stir and keep for 45 minutes, pour into the pre-prepared solution (12g water + 2g sodium bisulfite), stir, concentrate, concentrate and dry add 80g drinking water, pump After filtration, 3.3 g (82%) of white powder of the adduct was obtained, area content: 98.14%, purity (external standard method) 90.33%, MP: 217°C.

[0034] 2) Purification of decarboxylation oxide: In a 250ml three-necked flask, add 195g water, 9.9g sodium bicarbonate, stir to d...

Example Embodiment

[0036] Example 2:

[0037] A preparation method of 19-desmethyl-4-androstenedione, the preparation process is mainly composed of three parts: addition reaction, decarboxylation oxide purification, and alkali dereaction. The specific preparation method and steps are as follows:

[0038] 1) Addition reaction: In a 500ml three-necked flask, add 280g of acetone, 20g of rearrangement, stir to dissolve, turn on the freezer, cool to -34℃, add 30g of drinking water, between -35--40℃, Add (trichloroisocyanuric acid 6g + acetone 40g) solution dropwise, stir and keep for 45 minutes, pour into the pre-prepared (60g water + 10g sodium bisulfite) solution, stir, concentrate, concentrate and dry add 400g drinking water, suction filter , 17g (85%) of white-like powder of the adduct was obtained, area content: 99.10%, purity (external standard method) 91.43%, MP: 221°C.

[0039] 2) Purification of decarboxylation oxide: In a 500ml three-necked flask, add 390g water, 19.8g sodium bicarbonate, stir to...

Example Embodiment

[0041] Example 3:

[0042] A preparation method of 19-desmethyl-4-androstenedione, the preparation process is mainly composed of three parts: addition reaction, decarboxylation oxide purification, and alkali dereaction. The specific preparation method and steps are as follows:

[0043] 1) Addition reaction:

[0044] In a 1000ml three-necked flask, add 560g of acetone, 40g of rearrangement, stir to dissolve, turn on the freezer, cool to -34℃, add 60g of drinking water, add dropwise (trichloroisopropyl) between -35--40℃ Cyanuric acid 12g + acetone 80g) solution, stir and keep for 45 minutes, pour into the pre-prepared (120g water + 20g sodium bisulfite) solution, stir, concentrate, concentrate dry add 800g drinking water, suction filter, get the adduct 34g (85%) off-white powder, area content: 98.87%, purity (external standard method) 92.27%, MP: 219°C.

[0045] 2) Purification of decarboxylation oxide: In a 1000ml three-necked flask, add 780g water, 39.6g sodium bicarbonate, stir to d...

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 discloses a preparation method of 19-nor-4-androstenedione, which belongs to the technical field of medicine intermediate processing. The preparation process of the 19-nor-4-androstenedione includes three parts of addition reaction, decarboxylated oxide purification and alkali degreasing reaction, and the preparation method comprises the following steps of: firstly, with acetone as a solvent, dissolving a rearrangement product into the solvent, dropwise adding trichloroiminocyanuric acid, then concentrating to remove the acetone, adding water, and carrying out suction filtration to obtain an addition product; then adding the addition product of a decarboxylated oxide crude product by using the water as the solvent, enabling the addition product of the decarboxylated oxide crude product to become sodium salt through sodium bicarbonate, repeatedly washing off impurities with chloroform, and then enabling the sodium salt to become decarboxylated oxide through dilute hydrochloric acid; and finally, adding triethanolamine and a decarboxylated oxidation extract by using the acetone as the solvent, then adding the water for material precipitation, and carrying out suction filtration to obtain alkali degreasing white crystals. The invention has fewer adopted materials, low cost, simple preparation process, high reaction yield and high purity and quality of products and is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of 19-desmethyl-4-androstenedione. Background technique [0002] 19-desmethyl-4-androstenedione is the main intermediate in the synthesis of norethindrone and nandrolone phenylpropionate, among which: norethindrone is a progestin drug, which mainly promotes and maintains pregnancy and pregnancy It can be used for functional uterine bleeding, dysmenorrhea, irregular menstruation, endometriosis and infertility, etc. It can be used as a contraceptive when combined with estrogen drugs. [0003] China Pharmaceutical Research, Volume 15, No. 15, 2006, also reported a synthesis of 6 using 19-desmethyl-4-androstenedione as a starting material through etherification, reduction, diesterification and dehydrogenation steps. The method of 6-dehydronandrolone acetate, 6-dehydronandrolone acetate is a key intermediate for synthesizing medicines for w...

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
IPC IPC(8): C07J1/00
Inventor 王建国戴龙华
Owner 上海津力药业股份有限公司
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