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Method for preparing lubiprostone compound

A technology for lubiprostone and compounds, applied in organic chemistry, bulk chemical production, etc., can solve the problems of pressure-catalyzed hydrogenation, cumbersome reaction steps, difficult to complete conversion, etc., and achieve the improvement of reaction efficiency and purity, equipment The effect of low requirements and high reaction yield

Active Publication Date: 2015-04-29
QILU PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Adopted new route in CN103180306A, not only did not avoid pressurized catalytic hydrogenation, and reaction step is more loaded down with trivial details, also needs to use the relatively expensive dimethyl tert-butyl silyl ether, causes this route reaction period to be long, and cost is high, and product yield low rate
[0012] Although CN104140410A and CN103787942A disclose the process of adopting palladium-carbon atmospheric pressure catalytic reaction for 2 hours to prepare lubiprostone intermediate, the method of catalytic hydrogenation with hydrogen as hydrogen source under normal pressure is difficult to convert completely

Method used

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  • Method for preparing lubiprostone compound
  • Method for preparing lubiprostone compound
  • Method for preparing lubiprostone compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] At room temperature, add 0.5g (Z)-7-[(1R,2R,3R)-2-(4,4-difluoro-3-oxooctyl)-3-hydroxyl-5- Oxocyclopentyl]heptanoic acid-5-enbenzyl ester and 10ml methanol, add 0.1g of 10%Pd / C (50%H 2 O), then dilute 0.7g triethylsilane with 10ml methanol to make a solution, slowly drop it into the reaction flask, after the dropwise addition, keep the temperature of 15-25°C for 10 minutes, filter to remove palladium carbon, and concentrate the reaction solution Add 20ml of ethyl acetate, wash with 20ml of saturated sodium chloride, dry the organic layer over anhydrous sodium sulfate, concentrate the filtrate and evaporate to dryness to an oily substance to obtain lubiprostone. Weighing 0.39g, yield 97.5%, product purity 98.12%.

[0046] MS(m / z):389.46(M-1).

Embodiment 2

[0048] At room temperature, add 0.5g (Z)-7-[(1R,2R,3R)-2-(4,4-difluoro-3-oxooctyl)-3-hydroxyl-5- Oxocyclopentyl]heptanoic acid-5-enbenzyl ester and 10ml of ethanol, add 0.1g of 10%Pd / C (50%H 2 0), then dilute 0.7g triethylsilane with 10ml ethanol to form a solution, slowly drop it into the reaction bottle, after the dropwise addition, keep the reaction at 15-25°C for 30 minutes, remove palladium carbon by filtration, and concentrate the reaction solution Add 20ml of ethyl acetate, wash with 20ml of saturated sodium chloride, dry the organic layer over anhydrous sodium sulfate, filter, remove the desiccant, concentrate the filtrate and evaporate to dryness, weigh 0.39g, yield 97.5%. The product purity is 98.05%.

Embodiment 3

[0050]0.5g (Z)-7-[(1R,2R,3R)-2-(4,4-difluoro-3-oxooctyl)-3-hydroxyl-5-oxocyclopentyl]heptanoic acid Add -5-enbenzyl ester into methanol, stir to dissolve completely, add palladium hydroxide under nitrogen protection, add 0.7g triethylsilane to 10mL methanol to dilute, then add dropwise to the above solution for 10-15 minutes After dropping, react at 20-25°C for 30 minutes, remove palladium hydroxide by filtration, add 20mL of ethyl acetate after concentrating the reaction solution, wash once with 20mL of saturated sodium bicarbonate solution and 20mL of saturated sodium chloride, anhydrous sulfuric acid Sodium dry. After filtering and removing the desiccant, the filtrate was concentrated to obtain lubiprostone, weighing 0.375g, with a yield of 93.8% and a product purity of 97.93%.

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Abstract

The invention relates to a method for preparing lubiprostone. The method comprises the following steps: by taking triethyl silicane as a hydrogen source, and taking palladium carbon or palladium hydroxide as a catalyst, performing catalytic transfer hydrogenation, removing the protecting groups, and reducing double bonds, thereby obtaining the product. Compared with a conventional catalytic hydrogenation reaction at present, the method has the advantages of simplicity in operation, mild reaction conditions, high yield and high purity, the reaction time and reaction period are obviously shortened, the production efficiency is greatly improved, the requirements on reaction equipment are reduced, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and in particular relates to a preparation method of lubiprostone. Background technique [0002] Lubiprostone (lubiprostone) is a selective chloride ion channel activator that was jointly developed by Sucampo Pharms (Sucampo Company) in conjunction with Abbott and Takeda, and was launched in the United States in January 2006. The type 2 chloride ion channel on the luminal cell membrane promotes the secretion of intestinal juice and the peristalsis of the intestinal tract, and has the functions of lubricating the intestinal tract, softening the feces, and enhancing the peristaltic function of the gastrointestinal tract. It is clinically used to treat chronic idiopathic constipation in adults ( CIC), adult female patients over 18 years old (including) irritable bowel syndrome with constipation symptoms (IBS-C), and adult chronic non-cancer pain patients with opioid-induced co...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/94C07C405/00
CPCC07D311/94Y02P20/55
Inventor 田振平潘雷高源周晓东张贵岭范传文
Owner QILU PHARMA CO LTD
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