Preparation method of oxidation impurity

A technology for oxidizing impurities and oxidation reactions, applied in organic chemistry, steroids, etc., and can solve problems such as no relevant literature

Pending Publication Date: 2021-05-28
CHONGQING HUABANGSHENGKAI PHARM
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] Synthesis of 11β,16α,17α-trihydroxy-3-oxoandrost-1,4-diene-17-carboxylic acid ring 16,17-Acetal acetone There is no relevant literature, only similar reactions are reported for the preparation of 11β ,16α,17α,21,21-Pentahydroxypregna-1,4-diene-3,20-dione-16,17-acetal acetone, so the impurity ...

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Embodiment 1

[0045] Example 1 Preparation of 11β, 16α, 17α-trihydroxy-3-oxoandrost-1,4-diene-17-carboxylic acid ring 16,17-acetal acetone

[0046] Add 7.5g of desonide, 2300ml of tetrahydrofuran, 200ml of water, 5g of potassium hydroxide into a 3000ml three-neck flask, and let air flow in at 20-25°C for 16 hours. TLC spotting (CH2Cl2:CH3OH15:1) shows that the reaction of the raw materials is complete, stop To react, add 700ml of saturated brine / 500ml of ethyl acetate to separate layers, and concentrate the organic layer to dryness; add 700ml of ethyl acetate and 230ml of water, adjust the pH value to 2.5-3.5 with hydrochloric acid, separate the layers, and dry the organic layer with anhydrous sodium sulfate for 2 hours. Concentrate to dryness at 40-50°C, then dry under reduced pressure at 40-50°C for 4h to obtain 4.3g of solid, with HPLC purity of 98.2% ( figure 1 ), the integration results are shown in the table below, and the mass spectrum is shown in figure 2 .

[0047]

Embodiment 2

[0048] Example 2 Preparation of 11β, 16α, 17α-trihydroxy-3-oxoandrost-1,4-diene-17-carboxylic acid ring 16,17-acetal acetone

[0049] Add 7.5g of desonide, 2300ml of methanol, 200ml of water, and 3g of sodium hydroxide into a 3000ml three-necked flask, and feed air at 30-45°C for 19 hours. TLC spotting (CH2Cl2:CH3OH 15:1) shows that the reaction of the raw materials is complete. Stop the reaction, add 700ml saturated brine / 500ml ethyl acetate to separate layers, concentrate the organic layer to dryness; add 700ml ethyl acetate and 230ml water, adjust the pH value to 2.5-3.5 with hydrochloric acid, separate the layers, and dry the organic layer with anhydrous sodium sulfate for 2 hours , concentrated to dryness at 40-50° C., and then dried under reduced pressure at 40-50° C. for 4 hours to obtain 4.5 g of solid with an HPLC purity of 97.62%.

Embodiment 3

[0050] Example 3 Preparation of 11β, 16α, 17α-trihydroxy-3-oxoandrost-1,4-diene-17-carboxylic acid ring 16,17-acetal acetone

[0051] Add 7.5g of desonide, 2300ml of ethanol, 200ml of water, and 6g of lithium hydroxide into a 3000ml three-neck flask, and let air flow in at 10-15°C for 13 hours. TLC spotting (CH2Cl2:CH3OH 15:1) shows that the reaction of the raw materials is complete. Stop the reaction, add 700ml saturated brine / 500ml ethyl acetate to separate layers, concentrate the organic layer to dryness; add 700ml ethyl acetate and 230ml water, adjust the pH value to 2.5-3.5 with hydrochloric acid, separate the layers, and dry the organic layer with anhydrous sodium sulfate for 2 hours , concentrated to dryness at 40-50° C., and then dried under reduced pressure at 40-50° C. for 4 hours to obtain 3.8 g of solid, with an HPLC purity of 97.8%.

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Abstract

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of an oxidation impurity. The oxidation impurity is 11beta, 16alpha, 17alpha-trihydroxy-3-oxoandrostane-1, 4-diene-17-carboxylic acid ring 16, 17-acetal acetone, and the method comprises the following steps: taking desonide as a starting raw material, and introducing air to oxidize in the presence of inorganic alkali to obtain the oxidation impurity. The synthesis route is short, raw materials are easy to obtain, operation is simple, reaction conditions are mild, the impurity can be obtained without column chromatography, and the purity of the obtained impurity is 97% or above.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of oxidized impurities. Background technique [0002] Desonide is a glucocorticoid drug, which has anti-inflammatory, anti-allergic, anti-itching and reducing exudation effects; it can reduce and prevent tissue responses to inflammation, and can eliminate fever, redness and swelling caused by local non-infectious inflammation , thereby reducing the manifestations of inflammation; it has the immunosuppressive effect of preventing or inhibiting cellular immune response and suppressing the primary immune response. [0003] The chemical name of desonide is 11β,16α-17,21-tetrahydroxypregna-1,4-diene-3,20-dione ring 16,17-acetal acetone, and its structural formula (I) [0004] [0005] There are many impurities in desonide, one of which is oxidized impurity 11β,16α,17α-trihydroxy-3-oxoandrost-1,4-diene-17-carboxylic acid ring 16,17-acetal...

Claims

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Application Information

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IPC IPC(8): C07J71/00
CPCC07J71/0031
Inventor 陈小舟
Owner CHONGQING HUABANGSHENGKAI PHARM
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