Filtering liquid, preparation method thereof and application of filtering liquid in photocatalytic preparation of key intermediate of didrogesterone

Abstract

The invention relates to the technical field of medicine synthesis, and particularly discloses application of filtering liquid in photocatalytic preparation of a key intermediate of didrogesterone. The invention provides an application of a filtering solution in photocatalytic preparation of a key intermediate of didrogesterone. The filtering solution comprises a soluble copper salt, a soluble manganese salt and a soluble chromium salt as an aqueous solution of solutes, the key intermediate of the didrogesterone is 9beta, 10alpha-pregna-4, 6-diene-3, 20-diethylene glycol ketal. The filter liquid provided by the invention is applied to a reaction for preparing the key intermediate of the didrogesterone through photocatalysis, the yield of the key intermediate of the didrogesterone can be remarkably increased, the purity can reach 80.2%, the yield can reach 91.1%, and compared with a traditional filter sheet form, the production investment is lower, and large-scale industrial production of the key intermediate of the didrogesterone can be realized.

Description

Technical Field

[0001] The invention relates to the technical field of drug synthesis, and specifically discloses a filter liquid and a preparation method thereof, and application thereof in photocatalytic preparation of a key intermediate of dydrogesterone. Background Art

[0002] Dydrogesterone, chemically named 9β,10α-4,6-diene-3,20-dione, is a common oral progestogen in medical treatment. It belongs to steroid compounds and its main function is to regulate hormone levels. In clinical practice, it is mainly used to preserve pregnancy and prevent miscarriage, as well as various diseases caused by insufficient endogenous progesterone, such as dysmenorrhea, endometriosis, secondary amenorrhea, irregular menstrual cycle, dysfunctional uterine bleeding, premenstrual syndrome, threatened miscarriage or habitual miscarriage caused by progesterone deficiency, and infertility caused by corpus luteum deficiency. The structural formula of dydrogesterone is as follows:

[0003]

[0004] Compound 1 (chemical name: 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal) shown in formula I is a key intermediate in the preparation of dydrogesterone, which can be prepared by deprotection, double bond shift and other steps to obtain dydrogesterone, as shown below:

[0005]

[0006]

[0007] The compound 1 shown in formula I can be obtained by photocatalytic reaction of the compound 2 shown in formula II (chemical name: 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal), and the preparation route is as follows:

[0008]

[0009] In the prior art, the method for preparing compound 1 from compound 2 through photocatalytic reaction includes using LED light source of specific wavelength to irradiate for photochemical ring-opening and ring-closing reaction, and the photochemical ring-opening reaction needs to be carried out under irradiation of wavelength of 265-300nm, and the photochemical ring-closing reaction needs to be carried out under irradiation of wavelength of 305-365nm. However, it is very difficult to obtain luminescence in this wavelength band in the field of LED at present, and because the power of the light source cannot be increased, the cost of equipment investment and maintenance is high, and industrial production cannot be realized.

[0010] There are also methods of synthesizing compound 1 from compound 2 using dual-wavelength microflow technology, using a 500W or 1000W high-pressure mercury lamp as a light source for photocatalytic reaction, but the emission spectrum of the high-pressure mercury lamp is complex. If it is not selected during the reaction and the full spectrum is used for irradiation reaction, it will lead to many reaction by-products and slow reaction speed, thereby increasing the industrial production cost. Therefore, developing a preparation method of a diethylene glycol ketal compound with low industrial cost, fast reaction speed and industrial production is of great practical significance for improving the production efficiency of dydrogesterone. Summary of the invention

[0011] In view of the above problems, the present invention provides a filter liquid and a preparation method thereof, and an application of the filter liquid in the photocatalytic preparation of a key intermediate of dydrogesterone.

[0012] The first aspect of the present invention provides an application of a filter liquid in the photocatalytic preparation of a key intermediate of dydrogesterone, wherein the filter liquid is an aqueous solution with a soluble copper salt, a soluble manganese salt and a soluble chromium salt as solutes; the key intermediate of dydrogesterone is 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal.

[0013] Compared with the prior art, the filter liquid provided by the present invention selects soluble copper salt, soluble manganese salt and soluble chromium salt as solutes. The inventor unexpectedly discovered through a large number of experiments that when the soluble copper salt, soluble manganese salt and soluble chromium salt are used in combination as the solute of the filter liquid, the spectral composition, light intensity and wavelength of the light source to which the reaction substrate is exposed can be adjusted, the invalid light in the spectrum of the light source can be reduced, the photocatalytic reaction path can be optimized, the reaction substrate can be irradiated within a more suitable wavelength range, the yield of the key intermediate 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal of dydrogesterone can be improved, and the generation of reaction by-products can be reduced; the specific filter liquid can also effectively adjust the reflected light and scattered light of the light source, and the specific solute composition in the filter liquid can optimize the reaction conditions by redirecting the reflected light and scattered light to the reaction area, improve the stability and reaction efficiency of the reaction system, and thus improve the yield of the key intermediate 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal of dydrogesterone.

[0014] The filtered liquid provided by the present invention is used for photocatalytically preparing a key intermediate of dydrogesterone, 9β,10α-pregna-4,6-diene-3,20-diethylene glycol ketal. The yield of the key intermediate of dydrogesterone, 9β,10α-pregna-4,6-diene-3,20-diethylene glycol ketal, can be improved by adjusting the spectral composition, illumination intensity and wavelength of the irradiation light source and improving the stability of the reaction system. The purity of the filtered liquid can reach 80.2%, and the yield can reach 91.1%.

[0015] Preferably, the soluble copper salt is at least one of copper nitrate, copper chloride or copper sulfate.

[0016] Preferably, the soluble manganese salt is manganese chloride.

[0017] Preferably, the soluble chromium salt is at least one of chromium chloride or chromium sulfate.

[0018] Preferably, the concentration of the solute in the filtered liquid is 150 g / L-300 g / L.

[0019] Preferably, the mass ratio of the soluble copper salt, the soluble manganese salt and the soluble chromium salt in the solute is 1:(0.05-0.1):(0.05-0.1).

[0020] The present invention further limits the concentration of the solute, the mass ratio of the soluble copper salt, the soluble manganese salt and the soluble chromium salt, which is beneficial to further improve the yield of the key intermediate dydrogesterone 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal.

[0021] Preferably, in S2, the liquid depth of the filtered liquid is 2 cm-5 cm.

[0022] By limiting the depth of the filtered liquid, the yield of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal can be further improved.

[0023] The second aspect of the present invention provides a method for preparing the above-mentioned filter liquid, comprising the following steps: dissolving the soluble copper salt, the soluble manganese salt and the soluble chromium salt in water to obtain the filter liquid.

[0024] The third aspect of the present invention provides a method for preparing a key intermediate of dydrogesterone, comprising the following steps:

[0025] S1. In the presence of an organic solvent, an antioxidant and a stabilizer, a light source is used to perform a photochemical ring-opening reaction on the 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal shown in formula II to obtain intermediate I;

[0026] S2, irradiating the intermediate I with the light source after passing through the filter liquid to perform a photochemical ring-closing reaction to obtain the key intermediate dydrogesterone represented by formula I;

[0027] Wherein, the key intermediate of dydrogesterone is 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal;

[0028]

[0029] The preparation method provided by the present invention solves the problem that the existing key intermediate 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal of dydrogesterone cannot be industrially produced in large quantities, and compared with the traditional form of filter discs, the production investment is lower; and the yield of the preparation method provided by the present invention is significantly higher than that of the existing method, while improving the yield of the key intermediate 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal of dydrogesterone, the production cost of the key intermediate 9β,,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal of dydrogesterone can be further reduced, thereby reducing the production cost of the dydrogesterone product; the preparation method provided by the present invention not only has better stability, but also the prepared key intermediate 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal of dydrogesterone has better quality.

[0030] Preferably, in S1, the organic solvent is ethyl acetate or tetrahydrofuran.

[0031] Preferably, in S1, the antioxidant is 2,6-di-tert-butyl-p-cresol.

[0032] Preferably, in S1, the stabilizer is trimethylpyridine.

[0033] Preferably, in S1, the mass volume ratio of the 9α,10β-pregna-4,6-diene-3,20-diethylene glycol acetal and the organic solvent is 1 g:(80-150) mL.

[0034] Preferably, in S1, the mass ratio of the 9α,10β-pregna-4,6-diene-3,20-diethylene glycol ketal to the antioxidant is 1:(0.05-0.1).

[0035] Preferably, in S1, the mass ratio of the 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal to the stabilizer is 1:(0.05-0.1).

[0036] Preferably, in S1, the temperature of the photochemical ring-opening reaction is 10°C-20°C.

[0037] Preferably, in S1, the condition for the termination of the photochemical ring-opening reaction is that the content of the 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal no longer decreases.

[0038] Preferably, in S1, the light source is a high-pressure mercury lamp, and the power of the high-pressure mercury lamp is 490W-500W.

[0039] Preferably, in S2, the liquid depth of the filtered liquid is 2 cm-5 cm.

[0040] It should be further explained that the light source can be irradiated into the reaction system through the filter liquid to complete the photocatalytic reaction, and the distance between the light source and the reaction system is 2cm-5cm.

[0041] Preferably, in S2, the temperature of the photochemical ring-closing reaction is 10°C-20°C.

[0042] Preferably, in S2, the condition for the termination of the photochemical ring-closing reaction is that the content of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal no longer increases.

[0043] Preferably, in S2, after the photochemical ring-closing reaction is completed, the reactants need to be concentrated, crystallized for the first time, and the filtrate is crystallized for the second time after solid-liquid separation to obtain the key intermediate of dydrogesterone.

[0044] Further preferably, the conditions for the first crystallization are: adding methanol to the concentrate and stirring at a rate of 200 r / min-300 r / min for 1 h-1.5 h at room temperature.

[0045] Further preferably, the second crystallization is carried out under the conditions of adding methanol to the filtrate and stirring at a rate of 200 r / min-300 r / min for 2h-2.5h at -20°C to -15°C. DETAILED DESCRIPTION

[0046] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0047] Example 1

[0048] This embodiment provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, comprising the following steps:

[0049] S1. Add 100 g of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal, 8000 mL of ethyl acetate, 5 g of 2,6-di-tert-butyl-p-cresol and 5 g of trimethylpyridine into a chemical reactor, turn on a 500 W high-pressure mercury lamp for irradiation, and perform a photochemical ring-opening reaction at 10° C. When the content of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal no longer decreases, intermediate I is obtained;

[0050] S2, the light source is passed through the filter liquid with a depth of 2 cm, and the intermediate I is irradiated at 10°C to perform a photochemical ring-closing reaction. When the content of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal no longer increases, the reaction mixture is concentrated, methanol is added, and the mixture is stirred at a rate of 300 r / min for 1 hour at room temperature for crystallization. After solid-liquid separation, methanol is added to the filtrate, and the mixture is stirred at a rate of 200 r / min for 2 hours at -20°C for crystallization. The mixture is filtered to obtain 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal. Relative to the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal is 78.6%, and the yield is 91.1%;

[0051] The filter solution is an aqueous solution with copper nitrate, manganese chloride and chromium sulfate as solutes, the concentration of the solute in the filter solution is 150 g / L, and the mass ratio of copper nitrate, manganese chloride and chromium sulfate is 1:0.05:0.05.

[0052] Example 2

[0053] This embodiment provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, comprising the following steps:

[0054] S1. Add 100 g of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal, 15000 mL of tetrahydrofuran, 10 g of 2,6-di-tert-butyl-p-cresol and 10 g of trimethylpyridine into a chemical reactor, turn on a 500 W high-pressure mercury lamp for irradiation, and perform a photochemical ring-opening reaction at 20° C. When the content of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal no longer decreases, intermediate I is obtained;

[0055] S2, the light source is passed through the filter liquid with a depth of 5 cm, and the intermediate I is irradiated at 20°C to perform a photochemical ring-closing reaction. When the content of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal no longer increases, the reaction mixture is concentrated, methanol is added, and the mixture is stirred at a rate of 200 r / min for 1.5 hours at room temperature for crystallization. After solid-liquid separation, methanol is added to the filtrate, and the mixture is stirred at a rate of 300 r / min for 2.5 hours at -15°C for crystallization, and filtered to obtain 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal. Relative to the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal is 79.1%, and the yield is 89.3%;

[0056] The filtered solution is an aqueous solution with copper sulfate, manganese chloride and chromium sulfate as solutes, the concentration of the solutes in the filtered solution is 300 g / L, and the mass ratio of copper sulfate, manganese chloride and chromium sulfate is 1:0.1:0.1.

[0057] Example 3

[0058] This embodiment provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, comprising the following steps:

[0059] S1. Add 100 g of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal, 10000 mL of tetrahydrofuran, 7 g of 2,6-di-tert-butyl-p-cresol and 8 g of trimethylpyridine into a chemical reactor, turn on a 500 W high-pressure mercury lamp for irradiation, and perform a photochemical ring-opening reaction at 15° C. When the content of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal no longer decreases, intermediate I is obtained;

[0060] S2, the light source is passed through the filter liquid with a depth of 4 cm, and the intermediate I is irradiated at 16°C to perform a photochemical ring-closing reaction. When the content of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal no longer increases, the reaction mixture is concentrated, methanol is added, and the mixture is stirred at a rate of 300 r / min for 1.2 h at room temperature for crystallization. After solid-liquid separation, methanol is added to the filtrate, and the mixture is stirred at a rate of 300 r / min for 2.1 h at -17°C for crystallization, and filtered to obtain 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal. Relative to the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal is 80.2%, and the yield is 88.3%;

[0061] The filtered solution is an aqueous solution with copper chloride, manganese chloride and chromium sulfate as solutes, the concentration of the solutes in the filtered solution is 210 g / L, and the mass ratio of copper chloride, manganese chloride and chromium sulfate is 1:0.07:0.08.

[0062] Example 4

[0063] This embodiment provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, which is different from that of Example 1 in that the amount of copper nitrate is increased. Specifically:

[0064] The filter solution is an aqueous solution with copper nitrate, manganese chloride and chromium sulfate as solutes, the concentration of the solute in the filter solution is 150 g / L, and the mass ratio of copper nitrate, manganese chloride and chromium sulfate is 2:0.05:0.05;

[0065] The other components and operating steps are the same as those in Example 1.

[0066] Results: Based on the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal was 67.2%, and the yield was 81.6%.

[0067] Example 5

[0068] This embodiment provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, which is different from that of embodiment 1 in that the amount of manganese chloride is increased. Specifically:

[0069] The filter solution is an aqueous solution with copper nitrate, manganese chloride and chromium sulfate as solutes, the concentration of the solute in the filter solution is 150 g / L, and the mass ratio of copper nitrate, manganese chloride and chromium sulfate is 1:0.15:0.05;

[0070] The other ingredients and operating steps are the same as those in Example 1.

[0071] Results: Based on the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal was 73.5%, and the yield was 83.6%.

[0072] Example 6

[0073] This embodiment provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, which is different from that of embodiment 1 in that the depth of the filtered liquid is increased. Specifically:

[0074] S2, the light source is passed through the filter liquid with a depth of 8 cm, and the intermediate I is subjected to a photochemical ring-closing reaction at 10°C. When the content of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal no longer increases, the reaction mixture is concentrated, methanol is added, and the mixture is stirred at a rate of 300 r / min for 1 h at room temperature for crystallization. After solid-liquid separation, methanol is added to the filtrate, and the mixture is stirred at a rate of 200 r / min for 2 h at -20°C for crystallization, and filtered to obtain 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal;

[0075] The other components and operating steps are the same as those in Example 1.

[0076] Results: Based on the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal was 73.4%, and the yield was 78.2%.

[0077] Comparative Example 1

[0078] This comparative example provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, which is different from Example 1 in that copper nitrate is replaced by an equal amount of cadmium nitrate. Specifically:

[0079] The filter solution is an aqueous solution with cadmium nitrate, manganese chloride and chromium sulfate as solutes, the concentration of the solute in the filter solution is 150 g / L, and the mass ratio of cadmium nitrate, manganese chloride and chromium sulfate is 1:0.05:0.05;

[0080] The other components and operating steps are the same as those in Example 1.

[0081] Results: Based on the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal was 62.8%, and the yield was 61.3%.

[0082] Comparative Example 2

[0083] This comparative example provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, which is different from Example 1 in that manganese chloride is replaced by an equal amount of copper nitrate. Specifically:

[0084] The filter solution is an aqueous solution with copper nitrate and chromium sulfate as solutes, the concentration of the solute in the filter solution is 150 g / L, and the mass ratio of copper nitrate to chromium sulfate is 1.05:0.05.

[0085] The other components and operating steps are the same as those in Example 1.

[0086] Results: Based on the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal was 53.2%, and the yield was 68.8%.

[0087] Comparative Example 3

[0088] This comparative example provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, which is different from Example 1 in that copper nitrate is replaced by an equal amount of chromium sulfate. Specifically:

[0089] The filtered solution is an aqueous solution with manganese chloride and chromium sulfate as solutes, the concentration of the solute in the filtered solution is 150 g / L, and the mass ratio of manganese chloride to chromium sulfate is 0.05:1.05.

[0090] The other components and operating steps are the same as those in Example 1.

[0091] Results: Based on the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal was 19.8%, and the yield was 35.0%.

[0092] Comparative Example 4

[0093] This comparative example provides a method for preparing 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, which is different from Example 1 in that chromium sulfate is replaced by an equal amount of copper nitrate. Specifically:

[0094] The filter liquid is an aqueous solution with copper nitrate and manganese chloride as solutes, the concentration of the solute in the filter liquid is 150g / L, and the mass ratio of copper nitrate, manganese chloride and chromium sulfate is 1.05:0.05:.

[0095] The other components and operating steps are the same as those in Example 1.

[0096] Results: Based on the consumption of 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal, the purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal was 73.6%, and the yield was 72.9%.

[0097] By comparing Examples 1-6 and Comparative Examples 1-4, it can be seen that when the composition of the solute in the filtered liquid is changed outside the scope of the embodiments of the present invention, the purity and yield of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal prepared by the preparation method provided by the present invention are significantly reduced. This also proves that the use of the filtered liquid provided by the present invention can significantly improve the yield and purity of 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal, and the production investment is lower than that of the traditional filter plate form.

[0098] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. Application of a filtered liquid in the photocatalytic preparation of a key intermediate of dydrogesterone, characterized in that: The filtered solution is an aqueous solution with soluble copper salt, soluble manganese salt and soluble chromium salt as solutes; the key intermediate of dydrogesterone is 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol acetal.

2. The use of the filtered liquid according to claim 1 in the photocatalytic preparation of a key intermediate of dydrogesterone, characterized in that: The soluble copper salt is at least one of copper nitrate, copper chloride or copper sulfate; and / or The soluble manganese salt is manganese chloride; and / or The soluble chromium salt is at least one of chromium chloride or chromium sulfate.

3. The use of the filtered liquid according to claim 1 in the photocatalytic preparation of a key intermediate of dydrogesterone, characterized in that: The concentration of the solute in the filtered liquid is 150g / L-300g / L.

4. The use of the filtered liquid according to claim 3 in the photocatalytic preparation of a key intermediate of dydrogesterone, characterized in that: The mass ratio of the soluble copper salt, the soluble manganese salt and the soluble chromium salt in the solute is 1:(0.05-0.1):(0.05-0.1).

5. The use of the filtered liquid according to claim 1 in the photocatalytic preparation of a key intermediate of dydrogesterone, characterized in that: The liquid depth of the filter liquid is 2cm-5cm.

6. A method for preparing the filter liquid according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: dissolving the soluble copper salt, the soluble manganese salt and the soluble chromium salt in water to obtain a filtered liquid.

7. A method for preparing a key intermediate of dydrogesterone, characterized in that: The steps include: S1. In the presence of an organic solvent, an antioxidant and a stabilizer, a light source is used to perform a photochemical ring-opening reaction on the 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal shown in formula II to obtain intermediate I; S2, irradiating the intermediate I with the light source after passing through the filter liquid to perform a photochemical ring-closing reaction to obtain the key intermediate dydrogesterone represented by formula I; Wherein, the key intermediate of dydrogesterone is 9β,10α-pregnane-4,6-diene-3,20-diethylene glycol ketal; 8. The method for preparing the key intermediate of dydrogesterone according to claim 7, characterized in that: In S1, the organic solvent is ethyl acetate or tetrahydrofuran; and / or In S1, the antioxidant is 2,6-di-tert-butyl-p-cresol; and / or In S1, the stabilizer is trimethylpyridine.

9. The method for preparing the key intermediate of dydrogesterone according to claim 7, characterized in that: In S1, the mass volume ratio of the 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal and the organic solvent is 1 g: (80-150) mL; and / or In S1, the mass ratio of the 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol ketal to the antioxidant is 1:(0.05-0.1); and / or In S1, the mass ratio of the 9α,10β-pregnane-4,6-diene-3,20-diethylene glycol acetal to the stabilizer is 1:(0.05-0.1).

10. The method for preparing the key intermediate of dydrogesterone according to claim 7, characterized in that: In S1, the temperature of the photochemical ring-opening reaction is 10°C-20°C; and / or In S1, the light source is a high-pressure mercury lamp, and the power of the high-pressure mercury lamp is 490W-500W; and / or In S2, the liquid depth of the filtered liquid is 2 cm-5 cm; and / or In S2, the temperature of the photochemical ring-closing reaction is 10°C-20°C.

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