Method for synthesizing progesterone midbody 3beta-hydroxy-5-pregnene-20-ketone

A synthesis method and a pregnene technology are applied in the synthesis field of pharmaceutical intermediates, and can solve the problems of difficult control, large amount of active nickel in catalysts, etc., and achieve the effects of improving safety, reducing refining procedures, and facilitating reaction control.

Active Publication Date: 2015-01-07
HUAZHONG PHARMA
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In the traditional synthesis process of progesterone intermediate 3β-hydroxy-5-pregnene-20-one, it is difficult to control the production process of the catalytic hydrogenation process, and the amount of catalyst active nickel is too large, and excessive hydrogen absorption will inevitably occur, resulting in 20 The ketone group is converted to the unwanted C 20 (R), C 20 (S)-Hydroxyl mixture

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 synthesizing progesterone midbody 3beta-hydroxy-5-pregnene-20-ketone
  • Method for synthesizing progesterone midbody 3beta-hydroxy-5-pregnene-20-ketone
  • Method for synthesizing progesterone midbody 3beta-hydroxy-5-pregnene-20-ketone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1. Preparation of compound 3β-hydroxy-5,16-pregnadiene-3-acetate-20,20-ethylenedioxy (Ⅲ)

[0032] First, add 450kg of dichloromethane, 150kg of triethyl orthoformate, 150kg of ethylene glycol, 50kg of dienolone acetate, and 2.5kg of pyridine hydrochloride into the reactor, stir well and keep warm at 20°C React for 5 hours; after the reaction is completed, lower the temperature to below 5°C, start adding triethylamine dropwise, control the temperature at 5°C to 10°C, and stir for 30 minutes after adding; Methanol entrainment, after evaporating methanol to dryness, add 50kg of methanol and reflux for 30 minutes; under reflux, add 150kg of pure water dropwise, and then reflux for 1 hour after adding; cool down to below 5°C, continue to stir for 30 minutes, and let it stand for more than 2 hours , centrifuged to dry, washed with water and dried to obtain 55.7kg of compound (Ⅲ).

[0033] 2. Preparation of compound 3β-hydroxy-5-pregnene-3-acetate-20,20-ethylenedioxy (IV)

...

Embodiment 2

[0038]1. Preparation of compound 3β-hydroxy-5,16-pregnadiene-3-acetate-20,20-ethylenedioxy (Ⅲ)

[0039] First, 550kg of chloroform, 150kg of triethyl orthoformate, 180kg of ethylene glycol, 50kg of dienolone acetate, and 1.8kg of p-toluenesulfonic acid were added to the reactor, stirred evenly and placed in the reactor at 25 ℃ for 4 hours to react; after the reaction is completed, lower the temperature to below 5 ℃, start adding triethylamine dropwise, control the temperature at 5 ℃ ~ 10 ℃, and stir for 30 minutes after the addition; evaporate all solvents under reduced pressure, and then use Entrained with 20kg of methanol, evaporated to dryness, added 50kg of methanol and refluxed for 30 minutes; under reflux, added dropwise 150kg of pure water, and refluxed for 1 hour after addition; cooled to below 5°C, continued to stir for 30 minutes, and stood for 2 After more than 1 hour, it was centrifuged to dry, washed with water and dried to obtain 55.5kg of compound (Ⅲ).

[0040]...

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 relates to a method for synthesizing progesterone midbody 3beta-hydroxy-5-pregnene-20-ketone. By the method, a refining procedure and a by-product oxidation recovery processing procedure of a traditional synthesizing process are saved. The obtained midbody does not need to be refined, the once quality yield is more than 86%, and the product purity is more than 99.0%.

Description

technical field [0001] The invention relates to a method for synthesizing a pharmaceutical intermediate, in particular to a method for synthesizing a progesterone intermediate 3β-hydroxyl-5-pregnene-20-one. Background technique [0002] Progesterone (4-pregnene-3,20-dione) has the structural formula: [0003] [0004] Progesterone is a progestin drug and an important intermediate. The traditional synthesis process of progesterone intermediate 3β-hydroxy-5-pregnene-20-one is based on dienolone acetate as raw material, and 3β-hydroxy-5-pregnene is obtained in the presence of hydrogen and active nickel in ethanol. sterene-20-one-3-acetate, and then through alkali hydrolysis to obtain the crude product of the intermediate - 3β-hydroxy-5-pregnene-20-one, which contains about 5% impurities, and needs Refined to a content of 98.5% or more before the next step of the Wöhler oxidation reaction of progesterone. [0005] [0006] About 4% of the impurity in the crude 3β-hydrox...

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 Patents(China)
IPC IPC(8): C07J7/00
Inventor 王勇李新宇付林廖俊徐勇
Owner HUAZHONG 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