Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

The preparation method of 6β-methylprednisolone

A technology of methylprednisolone and methylene, which is applied in the field of compound preparation, can solve the problems of long synthetic route, danger, and low yield, and achieve the effects of low cost, easy control, and simple operation

Active Publication Date: 2022-06-14
TIANJIN PHARMA GROUP CORP
View PDF10 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Chinese patent CN107602652 discloses a method for preparing 6β-methylprednisolone, but the synthesis route is relatively long, and the route includes Grignard reaction, iodine reaction and biological dehydrogenation
In this patent, some 6β methyl products are prepared in the process of preparing 6α methyl, and the yield is low. This reaction method requires the presence of argon and hydrogen to participate in the reaction. The operation requires the use of an autoclave, which is inconvenient to operate Flammable and explosive is more dangerous, and in this invention the 6β methyl product exists in the form of impurities

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
  • The preparation method of 6β-methylprednisolone
  • The preparation method of 6β-methylprednisolone
  • The preparation method of 6β-methylprednisolone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] The preparation of embodiment 1 methylene intermediate

Embodiment 1-1

[0043] Dissolve 100 g of hydrocortisone in 1 L of ethanol, add 80 ml of triethyl orthoformate and 1 g of p-toluenesulfonic acid, stir at room temperature for 10 minutes, add 120 ml of 40% formaldehyde solution and 80 ml of N-methylaniline, stir at room temperature for 3 hours, add Concentrated hydrochloric acid adjusted the pH value of the reaction solution to 1-2, and kept stirring for 2 hours; the reaction solution was diluted into 3 L of water, the solid was precipitated, filtered with suction, and the filter cake was washed with water until neutral, and dried to obtain 98.5 g of a methylene intermediate with a molar yield of 98.5 g. The yield was 94.8%, and the HPLC purity was 95%.

Embodiment 1-2

[0045] Dissolve 36 g of hydrocortisone in 400 mL of methanol, add 45 ml of trimethyl orthoformate and 0.5 g of p-toluenesulfonic acid, stir at room temperature for 10 minutes, add 60 ml of 40% aqueous formaldehyde solution and 45 ml of N-methylaniline, and stir at room temperature for 3 hours. Add concentrated sulfuric acid to adjust the pH value of the reaction solution to 1-2, keep stirring for 2 hours; dilute the reaction solution into 1.5 L of water, separate out solids, filter with suction, wash the filter cake with water until neutral, and dry to obtain 35.1 g of methylene intermediate, The molar yield was 93.9%, and the HPLC purity was 94%.

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 for 6β-methylprednisolone, using hydrocortisone as a reaction starting material, through methylene reaction, reduction reaction, and dehydrogenation reaction to prepare 6β-methylprednisolone, comprising the following steps (1) methylene Reaction: Hydrocortisone reacts with an alkylating agent at a temperature of 0-50°C under the condition of a catalyst, then reacts with formaldehyde and N-methylaniline, and adjusts the pH value of the acidic condition to 1-2, and obtains methylene intermediate; (2) reduction reaction: under the catalysis of palladium carbon and monophosphite ligand, methylene intermediate reacts with cyclohexene heating to prepare the reduced product; (3) dehydrogenation reaction: the Reduction and dehydrogenation reagent, heat reflux reaction, 6β methylprednisolone. The beneficial effect of the present invention is that by adding a catalyst in the reduction reaction, 6β-methylprednisolone can be prepared through three steps of chemical reactions.

Description

technical field [0001] The invention relates to a new method for preparing a compound, in particular to a method for preparing 6β-methylprednisolone. Background technique [0002] Methylprednisolone belongs to the glucocorticoid class and is used for emergency treatment of critical illnesses, as well as for endocrine disorders, rheumatic diseases, collagen venereal diseases, skin diseases, allergic reactions, ophthalmic diseases, gastrointestinal diseases, blood diseases, leukemia, Shock, cerebral edema, polyneuritis, myelitis and prevention of vomiting caused by cancer chemotherapy. Currently, it is mainly used for organ transplantation in clinical practice. [0003] 6β-Methylprednisolone is an important impurity in finished methylprednisolone and has no pharmacological activity. In order to better control the quality of methylprednisolone, the impurities in it must be controlled, so it is necessary to prepare this substance as a reference substance. [0004] Chinese pat...

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): C07J5/00
CPCC07J5/0053
Inventor 陈伟李桢张成飞
Owner TIANJIN PHARMA GROUP CORP
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com