CN110790808A - Preparation method of 5, 7-pregnadiene-3, 20-diketone-diethylketal - Google Patents
Preparation method of 5, 7-pregnadiene-3, 20-diketone-diethylketal Download PDFInfo
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- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
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Abstract
The invention provides a preparation method of 5, 7-pregnadiene-3, 20-diketone-diethylketal, which comprises the following steps: under the action of a catalyst, progesterone and an etherification reagent generate an etherified substance through etherification reaction; the etherate and a dehydrogenation reagent generate 6-dehydroprogesterone through dehydrogenation reaction; the 6-dehydroprogesterone and ethylene glycol react to generate 5, 7-pregnadiene-3, 20-diketone-diethylketal through ketal under the action of a catalyst and a dehydrating agent. The invention can obtain 5, 7-pregnadiene-3, 20-diketone-diethylketal with less impurities through etherification, dehydrogenation and ketal reaction, has the advantages of short route, high yield, low raw material cost, simple operation and environmental protection, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of pharmacy, in particular to a preparation method of 5, 7-pregnadiene-3, 20-diketone-diethylketal.
Background
Dehydroprogesterone is a synthetic progestogen which, compared to naturally occurring progesterone (progesterone), has a trans-configuration and thus is abnormally stable during digestion, absorption and metabolism, and has very high oral activity, studies have found that steroids having the structure 9 β, 10a have a significant physiological effect compared to steroids having the structure 9a, 10 β, with double bonds between the carbon atoms 6 and 7, which has the two advantages of (1) increased metabolic stability for oral activity and (2) no side effects of androgens, estrogens and corticosteroids.
The 5, 7-pregnadiene-3, 20-diketone-diethylketal (compound III) is a key intermediate for synthesizing dehydroprogesterone, and the structural formula is as follows:
in the Journal of Organic Chemistry (1952),17, 1369-:
US patent No. 4464298 improves the above synthesis method by replacing NBS with dibromohydantoin, and the bromo product is isomerized with lithium bromide to convert most of the a-bromo product to β -bromo product, increasing the yield of the bromination reaction, and then debrominating with tetrabutylammonium fluoride monohydrate to obtain compound iii, the improved yield is greatly increased to 67.5% (purity 90%), tetrabutylammonium fluoride used in this route is monohydrate, which contains three crystal waters, and tetrabutylammonium fluoride trihydrate needs to be changed into tetrabutylammonium fluoride monohydrate by lyophilization, which greatly increases the production cost.
Chinese patent CN103314004 reports that progesterone is used as a starting material, two carbonyl groups are protected by ethylene glycol condensation, allyl position is selectively oxidized to obtain a 7-ketone compound, the 7-ketone compound reacts with p-toluenesulfonyl hydrazide to obtain hydrazone, and the compound III is obtained by removing hydrazone through Shapiro reaction. However, the method selectively performs allylic oxidation to prepare 7-ketone, generates more impurities and has low yield, so the method has little industrial significance. The synthetic route is as follows:
disclosure of Invention
In view of the above, the present invention provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, so as to solve the technical problems of more impurities, high production cost and great environmental pollution.
In view of the above objects, the present invention provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, comprising:
under the action of a catalyst, progesterone and an etherification reagent generate an etherified substance through etherification reaction;
the etherate and a dehydrogenation reagent generate 6-dehydroprogesterone through dehydrogenation reaction;
under the action of a catalyst and a dehydrating agent, the 6-dehydroprogesterone and ethylene glycol react through ketal to generate 5, 7-pregnadiene-3, 20-diketone-diethylketal;
wherein the structural formula of the etherate is shown in the specification
In some embodiments of the invention, the etherification agent is selected from one of trimethyl orthoformate, triethyl orthoformate, trimethyl orthoacetate, triethyl orthoacetate; the mass ratio of the etherification reagent to the progesterone is 0.3-1: 1.
In some embodiments of the present invention, the etherification reaction uses a catalyst selected from one of p-toluenesulfonic acid, perchloric acid, pyridine hydrochloride, and pyridine hydrobromide; the mass ratio of the catalyst to the progesterone is no more than 3%.
In some embodiments of the present invention, the etherification reaction is performed at a temperature of 0 to 30 ℃ for 1 to 6 hours.
In some embodiments of the present invention, the dehydrogenation reagent is selected from one of chloranil and 2, 3-dichloro-5, 6-dicyan-p-benzoquinone, and the mass ratio of the dehydrogenation reagent to the etherate is 0.3-2: 1.
In some embodiments of the present invention, the dehydrogenation reaction is performed at a temperature of 10 to 50 ℃ for 2 to 6 hours.
In some embodiments of the invention, the ketal reaction catalyst is selected from one of p-toluenesulfonic acid, perchloric acid, pyridine hydrochloride, pyridine hydrobromide; the mass ratio of the catalyst to the 6-dehydroprogesterone is no more than 5%.
In some embodiments of the invention, the dehydrating agent is selected from one of trimethyl orthoformate, triethyl orthoformate, trimethyl orthoacetate, triethyl orthoacetate.
In some embodiments of the invention, the mass ratio of the dehydrating agent to the 6-dehydroprogesterone is 0.5-2: 1.
In some embodiments of the present invention, the ketal reaction is performed at a temperature of 20 to 80 ℃ for 1 to 6 hours.
From the above, it can be seen that the preparation method of 5, 7-pregnadiene-3, 20-dione-diethyldiketal provided by the embodiment of the invention can obtain 5, 7-pregnadiene-3, 20-dione-diethyldiketal with less impurities through etherification, dehydrogenation and ketal reaction, has the advantages of short route, high yield, low raw material cost, simple operation and environmental protection, and is suitable for industrial production.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to specific embodiments below.
It is to be noted that technical terms or scientific terms used in the embodiments of the present invention should have the ordinary meanings as understood by those having ordinary skill in the art to which the present disclosure belongs, unless otherwise defined. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another.
The embodiment of the invention provides a preparation method of 5, 7-pregnadiene-3, 20-diketone-diethylketal, which comprises the following steps: under the action of a catalyst, progesterone and an etherification reagent generate an etherified substance through etherification reaction; the etherate and a dehydrogenation reagent generate 6-dehydroprogesterone through dehydrogenation reaction; the 6-dehydroprogesterone and ethylene glycol react to generate 5, 7-pregnadiene-3, 20-diketone-diethylketal (compound III) through ketal under the action of a catalyst and a dehydrating agent.
The reaction route is as follows:
wherein R is CH3Or C2H5。
According to the embodiment of the invention, the 5, 7-pregnadiene-3, 20-diketone-diethylketal with less impurities can be obtained through etherification, dehydrogenation and ketal reaction, and the method has the advantages of short route, high yield, low raw material cost, simplicity in operation and environmental friendliness, and is suitable for industrial production. The etherification reaction of the invention can selectively carry out 3-position etherification by controlling the reaction conditions, no 20-position etherification product is observed, the reaction impurities are less, and the yield is high. The dehydrogenation reaction only takes place 6,7 bit dehydrogenation, no 1,2 bit dehydrogenation product is observed, reaction impurities are few, and the yield is high by controlling the reaction conditions. And (3) ketal reaction, namely protecting the 3 and 20-site diketone by controlling reaction conditions, and obtaining the 5, 7-pregnadiene-3, 20-diketone-diethylketal with less impurity.
Optionally, the etherification reagent is selected from one of trimethyl orthoformate, triethyl orthoformate, trimethyl orthoacetate, triethyl orthoacetate; trimethyl orthoformate and trimethyl orthoacetate are preferred. The mass ratio of the etherification reagent to the progesterone is 0.3-1: 1. Alternatively, the etherification reaction may be carried out in an alcoholic organic solvent, preferably methanol or ethanol.
Optionally, the catalyst used in the etherification reaction is selected from one of p-toluenesulfonic acid, perchloric acid, pyridine hydrochloride and pyridine hydrobromide; p-toluenesulfonic acid and pyridine hydrochloride are preferred. The mass ratio of the catalyst to the progesterone is no more than 3%. Optionally, the reaction temperature of the etherification reaction is 0-30 ℃, and the reaction time is 1-6 hours.
Optionally, the dehydrogenation reagent is selected from one of chloranil and 2, 3-dichloro-5, 6-dicyan-p-benzoquinone, and chloranil is preferred. The mass ratio of the dehydrogenation reagent to the etherate is 0.3-2: 1. Alternatively, the dehydrogenation reaction may be carried out in a ketone-based organic solvent, preferably one of acetone and butanone. Optionally, the reaction temperature of the dehydrogenation reaction is 10-50 ℃, and the reaction time is 2-6 hours.
Optionally, the ketal reaction catalyst is selected from one of p-toluenesulfonic acid, perchloric acid, pyridine hydrochloride and pyridine hydrobromide; p-toluenesulfonic acid and pyridine hydrochloride are preferred. Optionally, the mass ratio of the catalyst to the 6-dehydroprogesterone is no more than 5%.
Optionally, the dehydrating agent is selected from one of trimethyl orthoformate, triethyl orthoformate, trimethyl orthoacetate, and triethyl orthoacetate, preferably trimethyl orthoformate and triethyl orthoformate. Optionally, the mass ratio of the dehydrating agent to the 6-dehydroprogesterone is 0.5-2: 1.
Optionally, the reaction temperature of the ketal reaction is 20-80 ℃, and the reaction time is 1-6 hours.
To aid in understanding the protocol of the present invention, several specific preparative procedures are set forth below. The various chemicals and reagents used in the examples were all commercially available unless otherwise specified.
Example 1:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which comprises the following steps:
step (1) etherification reaction
Adding 300ml of anhydrous methanol, 50g of progesterone and 30g of trimethyl orthoformate into a three-necked bottle, cooling to 0-5 ℃, adding 0.5g of p-toluenesulfonic acid, and reacting for 5-6 hours under the condition of heat preservation. TLC tracing reaction, after the reaction is finished, adding 1g of triethylamine, filtering, washing a filter cake with a small amount of methanol to obtain a methyl ether compound, wherein the wet weight is 69 g. Purity 98.2% (HPLC).
Step (2) dehydrogenation (preparation of 6-dehydroprogesterone)
300ml of acetone and 50ml of water, 45g of the methyl ether compound prepared in the example 1 and 45g of tetrachlorobenzoquinone are added into a three-neck flask, nitrogen is introduced to discharge air, and the temperature is raised to 40-45 ℃ for reaction for 3 hours. TLC detection raw material reaction is complete, poured into 1000ml water for water precipitation, filtered, washed and dried to obtain white solid 6-dehydroxanthone 46 g. The yield of 6-dehydroprogesterone prepared from progesterone is 92.6%, and the purity is 97.6%.
Step (3) ketal reaction
Adding 20g of 6-dehydroprogesterone, 80ml of ethylene glycol and 22ml of trimethyl orthoformate into a three-necked bottle, introducing nitrogen to exhaust air, adding 0.8g of p-toluenesulfonic acid, heating to 60-65 ℃ for reacting for 6 hours, detecting by TLC that raw materials are completely reacted, adding 1.5g of triethylamine, cooling to room temperature for crystallization for 2 hours, filtering, and washing a filter cake with a small amount of methanol to obtain a crude product of 5, 7-pregnadiene-3, 20-dione-diethylketal. Recrystallization was carried out with methanol to obtain 18.6g of a pale yellow compound, 5, 7-pregnadiene-3, 20-dione-diethylketal. Yield 72.5% and purity 97.1% (HPLC).
Example 2:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (1), 400ml of absolute ethyl alcohol, 50g of progesterone and 40g of triethyl orthoformate are added into a three-necked bottle, the temperature is reduced to 3-8 ℃, 1g of p-toluenesulfonic acid is added, and the reaction is carried out for 3-4 hours under the condition of heat preservation. TLC tracing reaction, after the reaction is finished, adding 2g of triethylamine, filtering, washing a filter cake with a small amount of ethanol to obtain an ether compound, wherein the wet weight is 73 g. Purity 97.5% (HPLC).
Example 3:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (1), 350ml of anhydrous methanol, 40g of progesterone and 40g of trimethyl orthoacetate are added into a three-necked bottle, the temperature is reduced to 10-15 ℃, 1g of perchloric acid is added, and the heat preservation reaction is carried out for 5-6 hours. TLC tracking reaction, after the reaction is finished, adding 2g of triethylamine, filtering, washing a filter cake with a small amount of methanol to obtain a methyl ether compound, wherein the wet weight is 57 g. Purity 97.9% (HPLC).
Example 4:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (1), 400ml of absolute ethyl alcohol, 45g of progesterone and 40g of triethyl orthoacetate are added into a three-necked bottle, the temperature is reduced to 1-6 ℃, 0.5g of pyridine hydrochloride is added, and the reaction is carried out for 1-2 hours under the condition of heat preservation. TLC tracing reaction, after the reaction is finished, adding 2g of triethylamine, filtering, washing a filter cake with a small amount of ethanol to obtain an ether compound, wherein the wet weight is 66 g. Purity 97.7% (HPLC).
Example 5:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (1), 380ml of absolute ethyl alcohol, 55g of progesterone and 35g of triethyl orthoacetate are added into a three-necked bottle, the temperature is reduced to 8-13 ℃, 1g of pyridine hydrobromide is added, and the reaction is carried out for 3-4 hours under the condition of heat preservation. And tracking the reaction by TLC, adding 2g of triethylamine after the reaction is finished, filtering, and washing a filter cake by using a small amount of ethanol to obtain an ether compound with the wet weight of 75 g. Purity 97.2% (HPLC).
Example 6:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (2), 200ml of butanone, 50ml of water, the ether compound prepared in the example 2 and 40g of chloranil are added into a three-necked bottle, nitrogen is introduced into the three-necked bottle to exhaust air, and the temperature is raised to 30-35 ℃ for reaction for 4 hours. TLC detects that the raw material completely reacts, and the raw material is poured into 1000ml of water for water precipitation, filtered, washed and dried to obtain 47.6g of white-like solid 6-dehydroprogesterone. The yield of 6-dehydroprogesterone prepared from progesterone is 95.8%, and the purity is 96.1%.
Example 7:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (2), 350ml of acetone, 60ml of water, 36g of the ether compound prepared in the example 2 and 36g of 2, 3-dichloro-5, 6-dicyan p-benzoquinone are added into a three-necked bottle, nitrogen is introduced into the bottle to exhaust air, and the temperature is raised to 45-50 ℃ for reaction for 1.5 hours. TLC detection raw material reaction is complete, pouring into 1000ml water for water precipitation, filtering, water washing and drying to obtain white solid 6-dehydroprogesterone 40.2 g. The yield of 6-dehydroprogesterone prepared from progesterone is 80.9%, and the purity is 95.2%.
Example 8:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (2), 400ml of butanone and 40ml of water, the methyl ether compound prepared in the example 1 and 44g of chloranil are added into a three-necked bottle, nitrogen is introduced into the three-necked bottle to exhaust air, and the temperature is raised to 20-30 ℃ for reaction for 5 hours. TLC detects that the raw material completely reacts, and the raw material is poured into 1000ml of water for elutriation, filtered, washed and dried to obtain 45.4g of white-like solid 6-dehydroprogesterone. The yield of 6-dehydroprogesterone prepared from progesterone is 91.4%, and the purity is 97.1%.
Example 9:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (2), 200ml of butanone and 50ml of water, 42g of the dimethyl ether compound prepared in the example 3 and 42g of 2, 3-dichloro-5, 6-dicyan p-benzoquinone are added into a three-necked bottle, nitrogen is introduced into the three-necked bottle to exhaust air, and the temperature is raised to 38-43 ℃ for reaction for 3 hours. TLC detection raw material reaction is complete, pouring into 1000ml water for water precipitation, filtering, water washing and drying to obtain white solid 6-dehydroprogesterone 34.1 g. The yield of 6-dehydroprogesterone prepared from progesterone is 85.8%, and the purity is 95.6%.
Example 10:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (3), 40g of 6-dehydroprogesterone, 200ml of ethylene glycol and 70ml of triethyl orthoformate are added into a three-necked bottle, nitrogen is introduced to exhaust air, 1.2g of p-toluenesulfonic acid is added, the temperature is increased to 65-70 ℃ for reaction for 5 hours, TLC is used for detecting that raw materials are completely reacted, 2g of triethylamine is added, the mixture is cooled to room temperature for crystallization for 2 hours, the mixture is filtered, and a filter cake is washed by a small amount of methanol to obtain a crude product of 5, 7-pregnadiene-3, 20-dione-diethyl ketal. Recrystallization from methanol gave 38.4g of the pale yellow compound 5, 7-pregnadiene-3, 20-dione-diethylketal. Yield 74.9% and purity 97.8% (HPLC).
Example 11:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (3), 35g of 6-dehydroprogesterone, 120ml of ethylene glycol and 50ml of trimethyl orthoacetate are added into a three-necked bottle, nitrogen is introduced to exhaust air, 1.3g of perchloric acid is added, the temperature is raised to 33-45 ℃ for reaction for 6 hours, TLC is used for detecting that raw materials are completely reacted, 2g of triethylamine is added, the mixture is cooled to room temperature for crystallization for 2 hours, the mixture is filtered, and a filter cake is washed by a small amount of methanol to obtain a crude product of 5, 7-pregnadiene-3, 20-dione-diethyl ketal. Recrystallization from methanol gave 25.4g of the pale yellow compound 5, 7-pregnadiene-3, 20-dione-diethylketal. The yield was 56.6% and the purity 98.3% (HPLC).
Example 12:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (3), 25g of 6-dehydroprogesterone, 100ml of ethylene glycol and 60ml of triethyl orthoformate are added into a three-necked bottle, nitrogen is introduced to exhaust air, 1.4g of pyridine hydrochloride is added, the temperature is raised to 75-80 ℃ for reaction for 2 hours, TLC is used for detecting that raw materials are completely reacted, 2.2g of triethylamine is added, the mixture is cooled to room temperature for crystallization for 2 hours, the mixture is filtered, and a filter cake is washed by a small amount of methanol to obtain a crude product of 5, 7-pregnadiene-3, 20-dione-diethyl ketal. Recrystallization from methanol gave 22.5g of the pale yellow compound 5, 7-pregnadiene-3, 20-dione-diethylketal. Yield 70.2% and purity 97.9% (HPLC).
Example 13:
this example provides a method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal, which differs from the preparation method of example 1 in that: in the step (3), 36g of 6-dehydroprogesterone, 150ml of ethylene glycol and 40ml of triethyl orthoacetate are added into a three-necked bottle, nitrogen is introduced to exhaust air, 1.7g of pyridine hydrobromide is added, the temperature is increased to 72-78 ℃ to react for 4 hours, TLC is used for detecting that the raw materials completely react, 1.7g of triethylamine is added, the mixture is cooled to room temperature to crystallize for 2 hours, the obtained product is filtered, and a filter cake is washed by a small amount of methanol to obtain a crude product of the compound III. Recrystallization from methanol gave 32.6g of the pale yellow compound 5, 7-pregnadiene-3, 20-dione-diethylketal. The yield was 70.6% and the purity 97.0% (HPLC).
The preparation method of the 5, 7-pregnadiene-3, 20-dione-diethyldiketal provided by the embodiment of the invention can obtain the 5, 7-pregnadiene-3, 20-dione-diethyldiketal with less impurities through etherification, dehydrogenation and ketal reaction, has the advantages of short route, high yield, low raw material cost, simple operation and environmental protection, and is suitable for industrial production.
Those of ordinary skill in the art will understand that: the discussion of any embodiment above is meant to be exemplary only, and is not intended to intimate that the scope of the disclosure, including the claims, is limited to these examples; within the idea of the invention, also technical features in the above embodiments or in different embodiments may be combined, steps may be implemented in any order, and there are many other variations of the different aspects of the invention as described above, which are not provided in detail for the sake of brevity.
The present embodiments are intended to embrace all such alterations, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, substitutions, improvements and the like that may be made without departing from the spirit and principles of the invention are intended to be included within the scope of the invention.
Claims (10)
1. A method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal is characterized by comprising the following steps:
under the action of a catalyst, progesterone and an etherification reagent generate an etherified substance through etherification reaction;
the etherate and a dehydrogenating agent generate 6-dehydroprogesterone through dehydrogenation reaction;
the 6-dehydroprogesterone and ethylene glycol react through ketal under the action of a catalyst and a dehydrating agent to generate 5, 7-pregnadiene-3, 20-diketone-diethylketal;
wherein the structural formula of the etherate is shown in the specification
2. The method for preparing 5, 7-pregnadiene-3, 20-dione-diethylketal according to claim 1, wherein the etherification agent is one selected from trimethyl orthoformate, triethyl orthoformate, trimethyl orthoacetate, and triethyl orthoacetate; the mass ratio of the etherification reagent to the progesterone is 0.3-1: 1.
3. The method for producing 5, 7-pregnadiene-3, 20-dione-diethylketal according to claim 1, wherein the etherification reaction is carried out using a catalyst selected from the group consisting of p-toluenesulfonic acid, perchloric acid, pyridine hydrochloride and pyridine hydrobromide; the mass ratio of the catalyst to the progesterone is no more than 3%.
4. The method for producing 5, 7-pregnadiene-3, 20-dione-diethylketal according to claim 1, wherein the etherification reaction is carried out at a reaction temperature of 0 to 30 ℃ for 1 to 6 hours.
5. The method for producing 5, 7-pregnadiene-3, 20-dione-diethylketal according to claim 1, wherein the dehydrogenation reagent is one selected from tetrachlorobenzoquinone and 2, 3-dichloro-5, 6-dicyan-p-benzoquinone, and the mass ratio of the dehydrogenation reagent to the etherate is 0.3 to 2: 1.
6. The method for producing 5, 7-pregnadiene-3, 20-dione-diethylketal according to claim 1, wherein the dehydrogenation reaction is carried out at a temperature of 10 to 50 ℃ for 2 to 6 hours.
7. The method for producing 5, 7-pregnadiene-3, 20-dione-diethylketal according to claim 1, wherein the ketal reaction catalyst is one selected from the group consisting of p-toluenesulfonic acid, perchloric acid, pyridine hydrochloride and pyridine hydrobromide; the mass ratio of the catalyst to the 6-dehydroprogesterone is no more than 5%.
8. The method for producing 5, 7-pregnadiene-3, 20-dione-diethylketal according to claim 1, wherein the dehydrating agent is one selected from trimethyl orthoformate, triethyl orthoformate, trimethyl orthoacetate, and triethyl orthoacetate.
9. The method for producing 5, 7-pregnadiene-3, 20-dione-diethylketal according to claim 8, wherein the mass ratio of the dehydrating agent to the 6-dehydroprogesterone is 0.5 to 2: 1.
10. The method of claim 1, wherein the reaction temperature of the ketal reaction is 20 to 80 ℃ and the reaction time is 1 to 6 hours.
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