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

Improvement preparation method for oxabolone cipionate

A technology of Oxybolon valeropropyl ester and alcohol cypionate, which is applied in the field of preparation of pharmaceutical compounds, can solve problems such as low product purity, severe reaction process, and serious environmental pollution, and achieve simple refining process and high product purity. High, the effect of improving the reaction yield

Active Publication Date: 2012-05-16
HUAZHONG PHARMA
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But in this method, a large amount of pyridine is used as the cyclopentapropionation reaction process product yield of solvent and catalyst is on the low side, and environmental pollution is serious, and because use a large amount of pyridine to cause the dissolution loss of intermediate product unavoidably, and the residual pyridine in the product is not easy Washing has a great impact on the appearance of the product and the next acidolysis reaction; the acidolysis process directly using concentrated sulfuric acid to participate in the reaction causes the reaction process to be too violent, and at the same time due to the strong oxidation of concentrated sulfuric acid, there are more by-products and the purity of the crude product Only more than 65%, it is not easy to purify, and the purity of the final product is not high. To obtain a high-purity product, multiple recrystallization or column separation methods must be used
The three-step total yield of epoxidation, cyclopentapropionation and acidolysis reported by this method is only 60%.

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
  • Improvement preparation method for oxabolone cipionate
  • Improvement preparation method for oxabolone cipionate
  • Improvement preparation method for oxabolone cipionate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] 1. Preparation of compound 19-desmethyl-4,5 epoxy-androst-3-one-17β-alcohol (III)

[0017] Add 300ml of methanol and 50g of 19-desmethyl-4-androsten-3-one-17-ol (II) to the reaction flask in turn and stir to dissolve at room temperature. Then cool down to 0°C, add dropwise a solution of 5g of sodium hydroxide dissolved in 28ml of water, drop the temperature to 0°C, and add 130ml of 25% hydrogen peroxide dropwise. After the addition was completed, the mixture was stirred and reacted at 0°C to 5°C for 2 hours, and then left to react for 16 hours. Cool down to -5°C, and add dropwise a solution of 70g of sodium bicarbonate dissolved in 350ml of water. Add 2200ml of water to it after the addition is complete, stir and cool down to within 5°C. Extract with 1000ml×2 ethyl acetate, wash neutral with water, and dry over anhydrous sodium sulfate. Concentrate under reduced pressure to a small volume, add pure benzene and continue to concentrate under reduced pressure to a small...

Embodiment 2

[0023] 1. Preparation of compound 19-desmethyl-4,5 epoxy-androst-3-one-17β-alcohol (III)

[0024] Add 900ml of methanol and 150g of 19-desmethyl-4-androsten-3-one-17-ol (II) to the reaction flask in turn, stirring and dissolving at room temperature. Then cool down to 0°C, add dropwise a solution of 15g of sodium hydroxide dissolved in 85ml of water, drop the temperature to 0°C, then add dropwise 345ml of 25% hydrogen peroxide. After the addition was completed, the reaction was stirred at 0°C to 5°C for 2 hours, and then allowed to stand for another 19 hours. Cool down to -5°C, add dropwise a solution of 200g of sodium bicarbonate dissolved in 1100ml of water. After the addition, 6500ml of water was added thereto, and the temperature was lowered to within 5°C with stirring. Extract with 2400ml×2 dichloromethane, wash neutral with water, and dry over anhydrous sodium sulfate. Concentrate under reduced pressure to a small volume, add pure benzene and continue to concentrate un...

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 an improvement preparation method for oxabolone cipionate. 19-demethyl-testosterone is taken as an initial raw material, the preparation method comprises the steps of epoxidation, cycrimine acidification and acidolysis, the acidolysis reaction uses dry hydrogen catalytic resin is taken as a catalyst. According to the invention, the preparation method enables by-products, the refining process is concise, the product purity can reach more than 99%. The reaction condition of the preparation method is mild, thereby the preparation method is beneficial to industrial production.

Description

technical field [0001] The present invention relates to a kind of preparation method of pharmaceutical compound, specifically a kind of Oxabolone pentapropyl ester (19-desmethyl-4-androstene-3-one-4β, 17β-diol-17-ring Improved preparation method of valeric acid ester). Background technique [0002] The structural formula of Oxabarolone Propyl Ester (19-desmethyl-4-androstene-3-one-4β, 17β-diol-17-cyclopentapropionate, CAS: 1254-35-9) is: [0003] [0004] Oxybolone valproate is an androgen compound and an important intermediate. [0005] In the U.S. invention patent US3020295, a method for synthesizing Oxybolon pentyl propyl ester is disclosed. The method uses 19-desmethyl-testosterone as a starting material, including three steps of epoxidation, cyclopentapropionation, and acidolysis. A large amount of pyridine is used as solvent and catalyst in the process of cyclopentapropionation reaction, and concentrated sulfuric acid is directly used to participate in the reactio...

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): C07J1/00B01J31/08
Inventor 王勇付林廖俊薛俊李桂莲
Owner HUAZHONG PHARMA