A photochemical reaction device for preparing 10α-methyl-steroidal compounds and its application

Abstract

The invention discloses a photochemical reaction device for preparing 10α-methyl-steroidal compounds, comprising: a photochemical conversion reactor for containing a reaction liquid to perform a photochemical conversion reaction; a light source for emitting broad-spectrum ultraviolet light; and a filter having a Cu-containing 2+ The filter liquid is arranged between the photochemical conversion reactor and the light source during the photochemical conversion reaction process, and the broad-spectrum ultraviolet light emitted by the light source is irradiated into the photochemical conversion reactor through the filter liquid for filtering. The present invention also provides the use of the above-mentioned photochemical reaction device in the synthesis of 10α-methyl-steroidal compounds. The photochemical reaction device of the present invention uses filters containing filter liquids with different concentrations of copper ions to filter the light source at different reaction stages, which is beneficial to obtaining ultraviolet light of specific requirements, and is beneficial to the photochemical conversion reaction, with few by-products and high yield.

Description

Technical Field

[0001] The invention belongs to the field of chemical synthesis, and in particular relates to a photochemical reaction device and application thereof. Background Art

[0002] Dydrogesterone, also known as dehydroprogesterone, has a chemical name of 9β,10α-pregnane-4,6-diene-3,20-dione, CAS number: 152-62-5, and the chemical formula is as follows:

[0003]

[0004] Dydrogesterone uses pregnane as the nucleus. Pregnane has the following skeleton structure, with four rings ABCD (from left to right, the four rings are defined as A, B, C and D, respectively). The carbon numbers (1-21) are as follows, which are recorded as C-1 position, C-2 position, etc. in the following text.

[0005]

[0006] Dydrogesterone is widely used for preserving pregnancy and preventing miscarriage, and is also widely used to treat various diseases caused by endogenous progesterone deficiency, such as dysmenorrhea, endometriosis, secondary amenorrhea, irregular menstrual cycle, dysfunctional uterine bleeding, premenstrual syndrome, threatened abortion or habitual abortion caused by progesterone deficiency, infertility caused by corpus luteum deficiency, etc.

[0007] At present, some synthetic routes of dydrogesterone start from ergosterol, synthesize 10α-configuration intermediates through photochemical synthesis, and then obtain dydrogesterone through several steps of chemical synthesis. The UV light source generally used in the photoconversion process of dydrogesterone intermediates is LED UV lamp. LED UV lamp has a single wavelength, low power (the power of a single lamp bead is about 3-5mW), and a limited range of wavelength selection (only 254nm, 265nm, 275nm, and 310nm UV light sources available on the market are available). Large-scale photochemical reactions require the integration of a large number of LED lamp beads, and the light source is complex to manufacture and very expensive.

[0008] Ultraviolet high-pressure mercury lamps can reach greater power (common industrial power 20kw), so the use of ultraviolet high-pressure mercury lamps can reduce costs and meet the light source requirements for the large-scale photochemical reaction of dydrogesterone intermediates. However, the spectral range of ultraviolet high-pressure mercury lamps is relatively wide (the ultraviolet region has a broad spectrum distribution at 250nm-370nm). Since the two-step photochemical reactions of dydrogesterone intermediates are respectively ring-opening and ring-closing reactions, they require specific wavelength ranges, which is contrary to the wide spectral range emitted by ultraviolet high-pressure mercury lamps, and is not conducive to the application of ultraviolet high-pressure mercury lamps in the large-scale photochemical reaction of dydrogesterone intermediates. Therefore, it is of great significance to propose a photochemical reaction device with controllable ultraviolet light source band for large-scale photochemical reaction of dydrogesterone intermediates. Summary of the invention

[0009] The technical problem to be solved by the present invention is to overcome the deficiencies and defects mentioned in the above background technology, and to provide a photochemical reaction device with a controllable ultraviolet light source band for preparing 10α-methyl-steroid compounds and its application. In order to solve the above technical problem, the technical solution proposed by the present invention is:

[0010] A photochemical reaction device for preparing 10α-methyl-steroidal compounds, comprising:

[0011] A photochemical conversion reactor, used to contain a reaction liquid for performing a photochemical conversion reaction;

[0012] a light source for emitting broad-spectrum ultraviolet light;

[0013] Filter, with Cu inside 2+ The filter liquid is arranged between the photochemical conversion reactor and the light source during the photochemical conversion reaction process, and the broad-spectrum ultraviolet light emitted by the light source is irradiated into the photochemical conversion reactor through the filter liquid for filtering;

[0014] The filter is configured to have a first state and a second state, which are used for the first stage and the second stage of the photochemical conversion reaction, respectively. In the first state, Cu 2+ The concentration is less than the Cu 2+ concentration;

[0015] Or the optical filter comprises a first optical filter and a second optical filter, which are used for the first stage and the second stage of the photochemical conversion reaction respectively, and the Cu 2+ The concentration is less than the Cu 2+ concentration.

[0016] In the above-mentioned photochemical reaction device, preferably, the conversion from the first state to the second state is achieved by adjusting or replacing the concentration of the filter liquid in the filter.

[0017] In the above-mentioned photochemical reaction device, preferably, the photochemical conversion reactor includes a first reactor and a second reactor, and the first filter and the second filter are respectively arranged for the first stage and the second stage of the photochemical conversion, and the reaction liquid can be introduced from the first reactor to the second reactor through a connecting pipeline. That is, the present invention adopts two sets of reaction equipment, which correspond to the first stage and the second stage of the photochemical conversion respectively.

[0018] In the above-mentioned photochemical reaction device, preferably, the optical filter is detachably arranged in the photochemical conversion reactor; the optical filter (referring to the first optical filter and the second optical filter) includes an inner shell and an outer shell, and a first closed area is formed between the inner shell and the outer shell for installing the filter liquid, and the interior of the inner shell is surrounded by a second semi-closed area for accommodating the light source. In the present invention, after the optical filter is arranged in the photochemical conversion reactor, a sealing cover is provided to seal the top of the photochemical conversion reactor. After the light source is set in the second semi-closed area, a sealing cover is also provided to seal the top of the second semi-closed area.

[0019] In the above-mentioned photochemical reaction device, preferably, a filter liquid cooling system is provided on the first closed area; the filter liquid cooling system includes a filter liquid inlet pipe, a filter liquid storage tank, a filter liquid outlet pipe, a filter liquid pump and a first cooling source, and both ends of the filter liquid inlet pipe and both ends of the filter liquid outlet pipe are respectively connected to the first closed area and the filter liquid storage tank to form a circulation loop, and the first cooling source and the filter liquid pump are arranged on the filter liquid inlet pipe and / or the filter liquid outlet pipe. Since the light source generates a large amount of heat, after it directly irradiates the filter liquid, the temperature of the filter liquid is too high, and a large amount of by-products will be generated. By setting up a filter liquid cooling system, it is convenient to maintain the temperature of the reaction system. The filter liquid pump preferably adopts a peristaltic pump, and the specific model of the first cooling source is not limited. For example, a cooling method of heat exchange of a cold jacket can be adopted.

[0020] In the above-mentioned photochemical reaction device, preferably, the photochemical conversion reactor is provided with a reaction liquid level stabilization system; the reaction liquid level stabilization system includes a reaction liquid inlet pipe, a reaction liquid storage tank, a reaction liquid outlet pipe and a reaction liquid pump, and the two ends of the reaction liquid inlet pipe and the two ends of the reaction liquid outlet pipe are respectively connected to the photochemical conversion reactor and the reaction liquid storage tank to form a circulation loop, and the reaction liquid pump is arranged on the reaction liquid inlet pipe. In the present invention, the reaction liquid outlet pipe is located above the photochemical conversion reactor, and the reaction liquid pump is arranged on the reaction liquid inlet pipe. When the reaction liquid overflows from the reaction liquid outlet pipe, the reaction liquid pump returns it to the photochemical conversion reactor. During the reaction process, the solvent will volatilize and lose, and the liquid level of the reaction liquid storage tank is observed to decrease. The reaction liquid level stabilization system can be used to conveniently add the reaction solvent, maintain the concentration of the reaction liquid, and facilitate the reaction.

[0021] In the above-mentioned photochemical reaction device, preferably, a second cooling system is provided on the outer wall of the photochemical conversion reactor; the second cooling system comprises a cooling jacket, a coolant inlet, a coolant outlet and a second cooling source provided on the outer wall of the photochemical conversion reactor, and both ends of the coolant inlet and the coolant outlet are respectively connected to the cooling jacket and the second cooling source. In order to further ensure the reaction temperature of the reaction liquid, the present invention is also provided with a second cooling system, and through the second cooling system, the second cooling source in the second cooling system can adopt a refrigerator with good refrigeration efficiency. The coolant inlet and the coolant outlet are respectively provided at the upper and lower ends of the cooling jacket.

[0022] In the above-mentioned photochemical reaction device, preferably, the Cu in the filter liquid used in the first stage 2+ The concentration of Cu in the filter liquid in the second stage is 0.1-0.5wt%. 2+ The concentration of Cu in the filter liquid used in the first stage is 0.5-1.2 wt%. More preferably, 2+ The concentration of Cu in the filter liquid in the second stage is 0.3-0.5wt%. 2+ The concentration is 0.7-1.0wt%.

[0023] In the above-mentioned photochemical reaction device, preferably, the filter liquid provides Cu 2+ The copper source is cupric chloride.

[0024] The filter liquid of the present invention contains Cu 2+ The filter liquid can be an aqueous solution or other solution that does not affect Cu 2+ Other filter effects can dissolve Cu 2+ Our research shows that different concentrations of Cu 2+ The light absorption characteristics are different. The use of a low concentration of filter liquid during the first stage of ring opening in the present invention is beneficial to the ring opening and the transformation to the desired configuration (if ultraviolet high-pressure mercury lamp is directly used for irradiation during the first stage of ring opening, the proportion of by-product configuration is very high due to the presence of unnecessary wavelengths (such as light with a wavelength of about 254nm), and the damage to the raw materials is reduced. The closed loop requires a higher concentration of filter liquid to strengthen the filtration of low wavelengths, so that the reaction equilibrium shifts toward the closed loop, and a higher yield can be obtained. The specific concentration of copper ion filter liquid used in the present invention, the filter liquid in the first stage can filter out part or all of the light with a wavelength less than 270nm (basically filters out light with a wavelength of about 254nm), and the filter liquid in the second stage can filter out part or all of the light with a wavelength less than 300nm. Our further research shows that providing Cu 2+ The copper source also has a certain influence on the filtering effect. Different types of anions will affect the filtering. More preferably, copper chloride is used as the source of Cu 2+The copper source, combined with the above-mentioned specific concentration, is more conducive to meeting the filtering effect required by the present invention than using copper sulfate, copper acetate, etc.

[0025] In the above-mentioned photochemical reaction device, preferably, the light source is an ultraviolet high-pressure mercury lamp, which generates light with some or all wavelengths within the range of 200-400nm. After the light source generated by the ultraviolet high-pressure mercury lamp of the present invention passes through the filter liquid, the filter liquid in the first stage filters out some or all light with a wavelength less than 270nm, and the filter liquid in the second stage filters out some or all light with a wavelength less than 300nm, which is beneficial to the requirements of the light source band at different stages when the reaction liquid reacts.

[0026] In the above-mentioned photochemical reaction device, preferably, a magnetic stirrer is provided at the bottom of the photochemical conversion reactor.

[0027] The "broad-spectrum ultraviolet light" of the present invention refers to ultraviolet light containing a wider wavelength range, relative to the single wavelength or single spectral peak of the LED ultraviolet lamp. For example, light containing part or all of the wavelengths in the range of 200-400nm, and another example is ultraviolet light with multiple spectral peaks in the range of 253-367nm. Under the above definition, an ultraviolet high-pressure mercury lamp is a light source that can emit broad-spectrum ultraviolet light. In view of the problem to be solved by the present invention, the broad-spectrum ultraviolet light at least includes part or all of the light with a wavelength less than 270nm (for example, light containing about 254nm), part or all of the light in the range of 270-300nm, and part or all of the light in the range of 300-350nm. The light source that can emit broad-spectrum ultraviolet light can also emit part of the light in other bands, such as visible light.

[0028] In order to better understand the above-mentioned photochemical reaction device, the present invention also provides an application of the above-mentioned photochemical reaction device in the synthesis of 10α-methyl-steroid compounds, so that the C-10 methyl group of the 5,7-diene steroid compound with a β-methyl group at the C-10 position is flipped to an α configuration. Specifically as follows: A preparation method of a 10α-methyl-steroid compound (an intermediate or raw material for synthesizing dydrogesterone) comprises the following steps: a 5,7-diene steroid compound with a β-methyl group at the C-10 position is subjected to photochemical conversion in a photochemical conversion reactor under the irradiation of a light source and filtering by a filter, so that the methyl group at the C-10 position is flipped from a β configuration to an α configuration; the different filtering requirements of the two stages of the reaction can be achieved by replacing the filter or replacing the filter liquid of the filter.

[0029] In the above application, the "two stages of photochemical conversion" generally include the following two stages in terms of mechanism (the approximate reaction process of the steroid ring skeleton is as follows): in the first stage, ring opening occurs under the irradiation of ultraviolet light in a certain wavelength range (generally 270-300nm), and in the second stage, ring closing occurs under the irradiation of ultraviolet light in another certain wavelength range (generally 300-350nm). In terms of macroscopic operation, the first stage is to irradiate with ultraviolet light in a certain wavelength range for a period of time, and the second stage is to irradiate with ultraviolet light in another certain wavelength range for another period of time. The irradiation time can be adjusted according to the specific reaction degree.

[0030]

[0031] The above-mentioned "5,7-diene steroid compound having a β-methyl group at the C-10 position" refers to a compound having a steroid skeleton in which the C-3 position and the C-17 position or other positions may be substituted by a substituent.

[0032]

[0033] The methyl group at the C-10 position is flipped from the β configuration to the α configuration to have the following steroid skeleton.

[0034]

[0035] There are many intermediates or raw materials for synthesizing dydrogesterone, such as ergosterol, etc. They all need to undergo photochemical conversion, and the mechanism of photochemical conversion is roughly the same, so the method of the present invention can be applied to such compounds.

[0036] Compared with the prior art, the advantages of the present invention are:

[0037] 1. The photochemical reaction device of the present invention uses filters containing copper ion-containing filter liquids of different concentrations to filter the light source at different reaction stages, which is beneficial to obtaining ultraviolet light of specific requirements, is beneficial to the photochemical conversion reaction, has few by-products, and has a high yield.

[0038] 2. The photochemical reaction device of the present invention allows the use of a light source that emits broad-spectrum ultraviolet light by providing an optical filter, which has a low cost and is conducive to the industrial production of dydrogesterone intermediates.

[0039] 3. The photochemical reaction device of the present invention has a simple structure, is easy to use, and has broad market application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0041] Figure 1 Schematic diagram of the structure of the photochemical reaction device used to prepare 10α-methyl-steroid compounds in Example 1.

[0042] Figure 2 Schematic diagram of the structure of the photochemical reaction device for preparing 10α-methyl-steroidal compounds in Example 2 (the reaction liquid level stabilization system and the second cooling system are not shown in the figure).

[0043] Legend:

[0044] 1. Photochemical conversion reactor; 2. Light source; 3. Filter; 4. Filter liquid inlet pipe; 5. Filter liquid storage tank; 6. Filter liquid outlet pipe; 7. Filter liquid pump; 8. First cooling source; 9. Reaction liquid inlet pipe; 10. Reaction liquid storage tank; 11. Reaction liquid outlet pipe; 12. Reaction liquid pump; 13. Cooling jacket; 14. Coolant inlet; 15. Coolant outlet; 16. Second cooling source; 17. Magnetic stirrer; 18. Connecting pipeline; 31. Inner shell; 32. Outer shell; 33. First closed area; 34. Second semi-closed area; 101. First reactor; 102. Second reactor; 301. First filter; 302. Second filter. DETAILED DESCRIPTION

[0045] In order to facilitate the understanding of the present invention, the present invention will be described more comprehensively and meticulously below in conjunction with the accompanying drawings and preferred embodiments of the present invention, but the protection scope of the present invention is not limited to the following specific embodiments.

[0046] Unless otherwise defined, all the professional terms used below have the same meanings as those generally understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention.

[0047] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0048] Embodiment 1:

[0049] like Figure 1 As shown, the photochemical reaction device for preparing 10α-methyl-steroidal compounds in this embodiment includes:

[0050] A photochemical conversion reactor 1, used for containing a reaction liquid to perform a photochemical conversion reaction;

[0051] A light source 2, for emitting broad-spectrum ultraviolet light;

[0052] Filter 3, with Cu inside 2+ The filter liquid is arranged between the photochemical conversion reactor 1 and the light source 2 during the photochemical conversion reaction process. The broad-spectrum ultraviolet light emitted by the light source 2 is irradiated into the photochemical conversion reactor 1 through the filter liquid for filtering.

[0053] The filter 3 is configured to have a first state and a second state, which are used for the first stage and the second stage of the photochemical conversion reaction respectively. In the first state, the Cu 2+ The concentration is less than the Cu 2+ concentration.

[0054] In this embodiment, the conversion from the first state to the second state is achieved by adjusting or replacing the concentration of the filter liquid in the filter 3 .

[0055] In this embodiment, the filter 3 is detachably arranged in the photochemical conversion reactor 1; the filter 3 includes an inner shell 31 and an outer shell 32, and a first closed area 33 is formed between the inner shell 31 and the outer shell 32 for installing the filter liquid, and the interior of the inner shell 31 is surrounded by a second semi-closed area 34 for accommodating the light source 2.

[0056] In this embodiment, a filter liquid cooling system is provided on the first closed area 33; the filter liquid cooling system includes a filter liquid inlet pipe 4, a filter liquid storage tank 5, a filter liquid outlet pipe 6, a filter liquid pump 7 (such as a peristaltic pump) and a first cooling source 8, both ends of the filter liquid inlet pipe 4 and both ends of the filter liquid outlet pipe 6 are respectively connected to the first closed area 33 and the filter liquid storage tank 5 to form a circulation loop, and the first cooling source 8 and the filter liquid pump 7 are provided on the filter liquid inlet pipe 4 and / or the filter liquid outlet pipe 6.

[0057] After the first stage reaction is completed, copper salt or a concentrated solution of copper salt is added to the filter liquid storage tank 5 to make the filter liquid in the filter 3 reach the Cu content required in the second stage. 2+ Concentration is fine.

[0058] In this embodiment, a reaction liquid level stabilization system is provided on the photochemical conversion reactor 1; the reaction liquid level stabilization system includes a reaction liquid inlet pipe 9, a reaction liquid storage tank 10, a reaction liquid outlet pipe 11 and a reaction liquid pump 12 (such as a peristaltic pump), and both ends of the reaction liquid inlet pipe 9 and both ends of the reaction liquid outlet pipe 11 are respectively connected to the photochemical conversion reactor 1 and the reaction liquid storage tank 10 to form a circulation loop, and the reaction liquid pump 12 is provided on the reaction liquid inlet pipe 9.

[0059] In this embodiment, a second cooling system is provided on the outer wall of the photochemical conversion reactor 1; the second cooling system includes a cooling jacket 13, a coolant inlet 14, a coolant outlet 15 and a second cooling source 16 provided on the outer wall of the photochemical conversion reactor 1, and both ends of the coolant inlet 14 and both ends of the coolant outlet 15 are connected to the cooling jacket 13 and the second cooling source 16 respectively.

[0060] In this embodiment, the Cu in the filter liquid used in the first stage 2+ The concentration of Cu in the filter liquid in the second stage is 0.1-0.5wt% (the above range is acceptable). 2+ The concentration is 0.5-1.2wt% (all within the above range).

[0061] In this embodiment, the filter liquid provides Cu 2+ The copper source is cupric chloride.

[0062] In this embodiment, the light source 2 is an ultraviolet high-pressure mercury lamp, which generates light with a partial or full wavelength within the range of 200-400 nm.

[0063] In this embodiment, a magnetic stirrer 17 is provided at the bottom of the photochemical conversion reactor 1 .

[0064] In this embodiment, the distance between the outer wall of the outer shell 32 and the inner wall of the photochemical conversion reactor 1 (i.e., the width of the reaction liquid) has a great influence on the reaction process. For a certain light source 2, the concentration of the reaction substrate (i.e., the 5,7-diene steroid compound with a β-methyl at the C-10 position) is certain. If the distance is too small, the specific wavelength emitted by the light source 2 cannot be completely absorbed by the reaction liquid, and the illumination efficiency will be very low. Therefore, the distance should be greater than a certain value to improve the illumination efficiency and reduce the cost.

[0065] In this embodiment, the power of the ultraviolet high-pressure mercury lamp is controlled to be 20kW, the concentration of the reaction substrate is 1g / 10mL, the distance is controlled to be greater than 5cm, and the concentration of the reaction substrate is 1g / 50mL, the distance is controlled to be greater than 10cm. If the power of the ultraviolet high-pressure mercury lamp is 500W, the concentration of the reaction substrate is 1g / 30mL, the distance is controlled to be greater than 2cm, and the concentration of the reaction substrate is 1g / 50mL, the distance is controlled to be greater than 3cm.

[0066] To be suitable for industrialization, the distance should generally be at least 2 cm. As the lamp power increases, the corresponding distance increases; as the concentration of the reaction substrate increases, the corresponding distance increases.

[0067] This embodiment also provides an application of the above-mentioned photochemical reaction device in the synthesis of 10α-methyl-steroid compounds. The specific application is as follows: the C-10 methyl group of a 5,7-diene steroid compound with a β-methyl group at the C-10 position is flipped to an α configuration (which can be used to prepare dydrogesterone). The specific steps are as follows:

[0068] Add 40g of compound A and 500mL of tetrahydrofuran to a photochemical reaction bottle, and first open the ring under irradiation of an ultraviolet high-pressure mercury lamp (500W) at 5-10°C. During the ring opening, filter with a filter liquid (1wt% cupric chloride aqueous solution), illuminate for 8 hours, and monitor by HPLC that the raw material: product = about 70:20. Filter with a filter liquid (copper chloride concentration 2wt%), continue to illuminate for 8h, monitor by HPLC, and stop when the raw material: product = about 55:35; concentrate the organic phase, replace it with methanol to a small volume, cool it to -20°C and freeze it for 4 hours, filter it, and dry it to obtain 16g of a white solid, which is mainly the raw material; concentrate the mother liquor, replace it with acetonitrile to a small volume and then discharge it, cool it to -20°C and freeze it for 4 hours, filter it, and dry it to obtain 9.8g of compound B as a white solid, with a one-time yield of about 24.5%.

[0069] A comparative test was carried out according to the above reaction steps and the reaction conditions in Table 1, and other conditions were the same as in this embodiment. The results are shown in Table 1 below.

[0070] Table 1: Experimental conditions and results

[0071] Open loop filtering Closed loop filtering One-time yield Comparative Example 1 No filter No filter 9% (the product will not precipitate) Comparative Example 2 1% Cupric Chloride Filter 1% Cupric Chloride Filter 20％ Comparative Example 3 1% copper acetate filter 2% copper acetate filter 22.5％ This embodiment 1% Cupric Chloride Filter 2% Cupric Chloride Filter 24.5％

[0072] In this embodiment, after testing, the NMR data of compound B is as follows: 1 HNMR(400MHz, CDCl3)δ7.78(d,J=8.3Hz,2H),7.34(d,J=8.1Hz,2H),5.66-5.64(m,1H),5.43–5.41(m,1H),4.09(s,1H),3.96(dd,J=9.3,3.1Hz ,1H),3.83(dd,J=9.3,6.0Hz,1H),2.49-2.45(m,5H),2.29-2.24(m,2H ),1.67–1.47(m,15H),0.97(d,J=6.7Hz,3H),0.72(s,3H),0.57(s,3H).

[0073] The photochemical steps in the above specific application are as follows:

[0074]

[0075] The 5,7-diene steroid compound having a β-methyl group at the C-10 position in this embodiment is

[0076]

[0077] The OTs group absorbs in the deep ultraviolet region and absorbs ultraviolet light in the deep ultraviolet region of the high-pressure mercury lamp, making this step of the reaction have a higher yield; at the same time, the presence of the OTs group makes the product easier to separate and reduces the complexity of post-processing.

[0078] Compound A is a new compound, and a synthetic route for preparing dydrogesterone using compound A is as follows. The synthetic route is short and has a high overall yield.

[0079]

[0080] Embodiment 2:

[0081] like Figure 2 As shown, the photochemical reaction device for preparing 10α-methyl-steroidal compounds in this embodiment includes:

[0082] A photochemical conversion reactor 1, used for containing a reaction liquid to perform a photochemical conversion reaction;

[0083] A light source 2, for emitting broad-spectrum ultraviolet light;

[0084] Filter 3, with Cu inside 2+ The filter liquid is arranged between the photochemical conversion reactor 1 and the light source 2 during the photochemical conversion reaction process. The broad-spectrum ultraviolet light emitted by the light source 2 is irradiated into the photochemical conversion reactor 1 through the filter liquid for filtering.

[0085] The optical filter 3 includes a first optical filter 301 and a second optical filter 302, which are used for the first stage and the second stage of the photochemical conversion reaction respectively. The Cu 2+ The concentration is less than the Cu in the filter liquid of the second filter 302. 2 + concentration.

[0086] In this embodiment, the photochemical conversion reactor 1 includes a first reactor 101 and a second reactor 102, which are respectively provided with a first filter 301 and a second filter 302, which are used for the first stage and the second stage of photochemical conversion. The reaction liquid can be introduced from the first reactor 101 into the second reactor 102 through a connecting pipe 18.

[0087] After the first stage reaction is completed, the reaction solution is introduced into the second reactor 102 to carry out the second stage reaction without adjusting the concentration of the filter solution.

[0088] The other components, structures and applications of this embodiment are the same as those of Embodiment 1.

Claims

1. A photochemical reaction device for preparing 10α-methyl-steroidal compounds, characterized in that: include: A photochemical conversion reactor (1) is used to contain a reaction liquid for performing a photochemical conversion reaction; A light source (2) for emitting broad-spectrum ultraviolet light; The filter (3) has a Cu 2+ A filter liquid is arranged between the photochemical conversion reactor (1) and the light source (2) during the photochemical conversion reaction process, and the broad-spectrum ultraviolet light emitted by the light source (2) is irradiated into the photochemical conversion reactor (1) through the filter liquid for filtering; The optical filter (3) comprises a first optical filter (301) and a second optical filter (302); the photochemical conversion reactor (1) comprises a first reactor (101) and a second reactor (102), the first optical filter (301) and the second optical filter (302) being respectively arranged to be used in the first stage and the second stage of photochemical conversion, and the reaction liquid is introduced from the first reactor (101) into the second reactor (102) via a connecting pipeline (18); The Cu in the filter liquid of the first filter (301) 2+ The concentration of Cu in the filter liquid of the second filter (302) is 0.1-0.5wt%, which is used to filter out part or all of the light with a wavelength less than 270nm. 2+ The concentration is 0.7-1wt%, which is used to filter out part or all of the light with a wavelength less than 300nm.

2. The photochemical reaction device according to claim 1, characterized in that: The optical filter (3) is detachably arranged in the photochemical conversion reactor (1); the optical filter (3) comprises an inner shell (31) and an outer shell (32); a first closed area (33) is formed between the inner shell (31) and the outer shell (32) for accommodating the optical filter liquid; and a second semi-closed area (34) is enclosed inside the inner shell (31) for accommodating the light source (2).

3. The photochemical reaction device according to claim 2, characterized in that: A filter liquid cooling system is provided on the first closed area (33); the filter liquid cooling system comprises a filter liquid inlet pipe (4), a filter liquid storage tank (5), a filter liquid outlet pipe (6), a filter liquid pump (7) and a first cooling source (8); both ends of the filter liquid inlet pipe (4) and both ends of the filter liquid outlet pipe (6) are respectively connected to the first closed area (33) and the filter liquid storage tank (5) to form a circulation loop; the first cooling source (8) and the filter liquid pump (7) are provided on the filter liquid inlet pipe (4) and / or the filter liquid outlet pipe (6).

4. The photochemical reaction device according to claim 1, characterized in that: The photochemical conversion reactor (1) is provided with a reaction liquid level stabilization system; the reaction liquid level stabilization system comprises a reaction liquid inlet pipe (9), a reaction liquid storage tank (10), a reaction liquid outlet pipe (11) and a reaction liquid pump (12); both ends of the reaction liquid inlet pipe (9) and both ends of the reaction liquid outlet pipe (11) are respectively connected to the photochemical conversion reactor (1) and the reaction liquid storage tank (10) to form a circulation loop; the reaction liquid pump (12) is arranged on the reaction liquid inlet pipe (9) and / or the reaction liquid outlet pipe (11).

5. The photochemical reaction device according to claim 1, characterized in that: The filter liquid provides Cu 2+ The copper source is cupric chloride.

6. The photochemical reaction device according to claim 1, characterized in that: The light source (2) is an ultraviolet high-pressure mercury lamp, which generates light with a partial or full wavelength in the range of 200-400 nm.

7. Use of the photochemical reaction device according to any one of claims 1 to 6 in the synthesis of 10α-methyl-steroidal compounds, wherein the C-10 methyl group of the 5,7-diene steroidal compound having a β-methyl group at the C-10 position is flipped to an α configuration through a photochemical conversion reaction; The photochemical conversion reaction includes the following two stages: in the first stage, ring opening occurs under the irradiation of ultraviolet light in a certain wavelength range, and in the second stage, ring closing occurs under the irradiation of ultraviolet light in another certain wavelength range.

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