Synthetic method of fulvestrant intermediate

A technology of fulvestrant and a synthesis method, which is applied in the synthesis field of estratane-triene-diol compounds, can solve the problems of large influence, complicated post-processing, etc., so as to simplify the production process and improve the product yield and quality, the effect of reducing environmental pollution

Active Publication Date: 2019-09-10
连云港恒运药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] Lithium bromide and copper bromide are used as dehydrogenation reagents in the prior art. Due to the use of a large amount of heavy metal reagents, the impact on the environment is relatively large, and the post-treatment is cumbersome.

Method used

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  • Synthetic method of fulvestrant intermediate
  • Synthetic method of fulvestrant intermediate
  • Synthetic method of fulvestrant intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022]

[0023] Add 10.7g of the compound of formula I with a purity of 98.4% to the reaction flask, add 200ml of acetonitrile, 7.0g of pyridinium bromide perhydrogen perbromide, and stir for 1 hour at 20-25°C. After the reaction is complete, add 60ml of 1mol / L lithium hydroxide aqueous solution, heat at 50-60°C for 2 hours, cool down, filter out the precipitate, concentrate the filtrate under reduced pressure to obtain an oil, add 200ml of ethyl acetate, 50ml of saturated saline, stir and separate , the organic phase was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 10.1 g of the compound of formula II with a purity of 98.5%.

Embodiment 2

[0025]

[0026] Add 10.7g of the compound of formula I with a purity of 98.4% to the reaction flask, add 200ml of acetonitrile, 7.7g of pyridinium bromide perhydrogen perbromide, and stir at 20-25°C for 1 hour. After the reaction is complete, add 60ml of 1mol / L lithium hydroxide aqueous solution, heat at 50-60°C for 2 hours, cool down, filter out the precipitate, concentrate the filtrate under reduced pressure to obtain an oil, add 200ml of ethyl acetate, 50ml of saturated saline, stir and separate , the organic phase was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 9.8 g of the compound of formula II with a purity of 98.4%.

Embodiment 3

[0028]

[0029] Add 10.7g of the compound of formula I with a purity of 98.4% to the reaction flask, add 200ml of acetonitrile, 7.7g of pyridinium bromide perhydrogen perbromide, and stir for 2 hours at 0-15°C. After the reaction is complete, add 60ml of 1mol / L lithium hydroxide aqueous solution, heat at 50-60°C for 2 hours, cool down, filter out the precipitate, concentrate the filtrate under reduced pressure to obtain an oil, add 200ml of ethyl acetate, 50ml of saturated saline, stir and separate , the organic phase was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 9.9 g of the compound of formula II with a purity of 98.3%.

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Abstract

The invention relates to a preparation method for a fulvestrant midbody. The method specifically comprises the following steps: adding pyridinium bromide perbromide into a compound shown as formula I and dehydrogenizing, and then adding lithium hydroxide into a reaction liquid and reacting, thereby acquiring a compound shown as formula II. According to the invention, pyridinium bromide perbromide is used as a dehydrogenizing agent, one-pot continuous reaction is adopted for realizing dehydrogenizing and bromination two-step reaction, the production technology is simplified, the product yield and quality are promoted, the use of heavy metal reagents, such as copper, is avoided and the environmental pollution is reduced.

Description

technical field [0001] The invention relates to a method for synthesizing a fulvestrant intermediate, that is, an estrane-triene-diol compound. Background technique [0002] Fulvestrant, molecular formula C 32 h 47 f 5 o 3 S, the chemical name is 7-α-[9-(4,4,5,5,5-pentafluoropentasulfinyl)nonyl]estra-1,3,5-(10)-triene- 3,17-β-diol, the structural formula is as follows: [0003] [0004] The preparation method of fulvestrant can be summarized into two general directions at present: one is to carry out a series of reactions with the more expensive dehydronandrolone acetate as the mother nucleus to obtain fulvestrant; the other is to use estradiol as the Derivatives of starting materials are used as nuclei to prepare fulvestrant. In both directions, 4,4,5,5,5-pentafluoropentanol, which is relatively expensive, must be used. [0005] [0006] Patent WO2006015081 describes the preparation of fulvestrant, which uses nandrolone as raw material, through acetylation reac...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J1/00
Inventor 冯芮茂张丰盈丁丹丹张庆捷
Owner 连云港恒运药业有限公司
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