CN114634542A - Preparation method of dehydronandrolone acetate - Google Patents

Abstract

The invention provides a preparation method of dehydronandrolone acetate, which comprises the following steps: the preparation method of the dehydro-nandrolone acetate improves the problem that an intermediate is easy to deteriorate to form impurities in the preparation process of dehydronandrolone acetate, and the preparation method is more efficient, high in product yield and low in impurity content.

Description

Preparation method of dehydronandrolone acetate

Technical Field

The invention relates to the technical field of drug intermediates, in particular to a preparation method of dehydronandrolone acetate.

Background

Dehydronandrolone acetate is a key intermediate for synthesizing two steroid medicines of fulvestrant and tibolone.

Dehydronandrolone acetate of formula C₂₀H₂₆O₃CAS registry number 2590-41-2, chemical name 17 beta hydroxy-estra-4, 6 dien-3-one. At present, dehydronandrolone acetate has three synthesis processes, one is prepared by using nandrolone as a starting material and performing 6, 7-site double esterification dehydrogenation; the second one is thatThe acid-removed substance is used as an initial raw material, and is prepared by 6, 7-position dehydrogenation after etherification hydroboration reduction and double esterification; the third one is prepared with nandrolone as initial material and through 3-site esterification, hydroboration reduction, 17-site esterification and 6-7-site dehydrogenation. The three processes are all prepared by 6-position and 7-position dehydrogenation, and in the classical process, bromine is unstable, and the bromine is easy to deteriorate at the temperature of more than 30 ℃ to generate other substances, so that the three processes have certain limitations.

In view of the above, how to provide a new preparation method to improve the content of impurities in the 6, 7-position dehydrogenation process and increase the yield of the target product is a technical problem that needs to be solved at present.

Disclosure of Invention

In view of this, the invention provides a preparation method of dehydronandrolone acetate capable of effectively reducing the generation amount of impurities in the 6, 7-position dehydrogenation process.

The technical scheme of the invention is realized as follows: the invention provides a preparation method of dehydronandrolone acetate, which comprises the following steps:

s1, preparing a first microchannel reactor loaded with a first catalyst, wherein the first catalyst is palladium and silver;

s2, preparing a second microchannel reactor loaded with a second catalyst, wherein the second catalyst is iron and aluminum;

s3, mixing androstane-3, 5-diene-17 beta-alcohol-3-acetate with DMF to obtain a first solution, mixing liquid bromine with DMF to obtain a second solution, respectively pumping the first solution and the second solution into a first microchannel reactor, keeping the temperature in the first microchannel reactor at 0-10 ℃ and the pressure at 0.2-0.4MPa, and collecting reaction liquid discharged from the first microchannel reactor;

s4, preparing an ethanol solution of sodium hydroxide, pumping the reaction liquid discharged from the first microchannel reactor and the ethanol solution of sodium hydroxide into a second microchannel reactor, keeping the temperature in the microchannel reactor at 0-10 ℃ and the pressure at 0.1-0.3MPa, and collecting the reaction liquid discharged from the second microchannel reactor;

s5, pumping the reaction liquid discharged from the second microchannel reactor, mixed liquid of acetic anhydride and triethylamine into a third microchannel reactor respectively, keeping the temperature in the third microchannel reactor at 0-10 ℃ and the pressure at 0.1-0.3MPa, and collecting the reaction liquid discharged from the third microchannel reactor;

and S6, washing the reaction solution discharged from the third microchannel reactor to be neutral by using a saturated sodium bicarbonate solution, standing for layering, taking an organic layer, and concentrating the organic layer to be dry to obtain the dehydronandrolone acetate.

On the basis of the above technical solution, preferably, in step S1, the method for preparing the first microchannel reactor loaded with the first catalyst includes:

s11, respectively mixing a water-soluble compound of palladium, a water-soluble compound of silver, terephthalic acid and water to obtain a mixed solution, heating the mixed solution to 50-60 ℃ by microwave under the ultrasonic condition, and stirring for 30-60min to obtain a precursor solution;

s12, drying the precursor solution to be in a powder state to obtain carrier powder;

and S13, uniformly mixing the carrier powder and the binder, and firing and forming to obtain the first microchannel reactor.

On the basis of the above technical solution, preferably, the water-soluble compound of palladium is palladium chloride or palladium nitrate, the water-soluble compound of silver is silver nitrate, and the water-soluble compound of palladium: water-soluble compound of silver: terephthalic acid: the mass ratio of water is 1: (2-4): (1-2): (100-500).

On the basis of the above technical solution, preferably, the binder is a mixture of alumina and aluminum powder, and the carrier powder: alumina: the mass ratio of the aluminum powder is 1: (1-3): (0.1-0.3).

On the basis of the technical scheme, preferably, the mass ratio of the androstane-3, 5-diene-17 beta-alcohol-3-acetic ester to the liquid bromine is 1: (1.2-1.4).

On the basis of the technical scheme, preferably, the mass ratio of the androstane-3, 5-diene-17 beta-alcohol-3-acetic ester to the sodium hydroxide is 1: (0.5-0.7).

On the basis of the technical scheme, preferably, the mass ratio of the androstane-3, 5-diene-17 beta-alcohol-3-acetic ester to acetic anhydride and triethylamine is 1: (1.5-1.8): (0.1-0.2).

On the basis of the above technical solution, preferably, in step S2, the method for preparing the second microchannel reactor supporting the second catalyst includes:

s21, mixing ferric chloride, aluminum chloride and water respectively, and ultrasonically stirring for 10-30min under the ultrasonic condition to obtain a mixed solution;

s22, dropwise adding ammonia water into the mixed solution obtained in the step S21 until white suspended matters appear in the solution, stopping dropwise adding, and drying the mixed solution to obtain carrier powder;

and S23, uniformly mixing the carrier powder and the binder, and firing and forming to obtain the second microchannel reactor.

On the basis of the above technical solution, preferably, the binder is zinc oxide, and the mass ratio of the carrier powder to the zinc oxide is 1: (2-3).

Compared with the prior art, the preparation method of dehydronandrolone acetate has the following beneficial effects:

(1) in the preparation process of dehydronandrolone acetate, androstane-3, 5-diene-17 beta-alcohol-3-acetate is taken as a raw material and is easily oxidized to generate impurities in the process of bromine addition, and the impurities are easily generated in the case of overhigh temperature under the conventional reaction condition;

(2) this application still adopts the microchannel reactor to replace other reaction processes, and reaction rate promotes by a wide margin to reduce unnecessary side reaction in the reaction process, further improved the product quality of dehydronandrolone acetate.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention.

Example 1.

Respectively weighing 1 part of palladium chloride, 2 parts of silver nitrate, 1 part of terephthalic acid and 100 parts of water, mixing, heating to 50 ℃ by microwave under the ultrasonic condition, stirring for 30min to obtain a precursor solution, and drying the precursor solution to be powdery.

Weighing 1 part of precursor powder, 1 part of alumina and 0.1 part of aluminum powder, uniformly mixing, filling into a mold, and firing to obtain a first microchannel reactor;

respectively weighing 1 part of ferric chloride, 1 part of aluminum chloride and 100 parts of water, stirring for 10min under the ultrasonic condition to obtain a mixed solution, dropwise adding ammonia water into the mixed solution until white suspended matters appear in the solution, stopping dropwise adding, drying the mixed solution to obtain carrier powder, weighing 1 part of carrier powder and 2 parts of zinc oxide powder, uniformly mixing, filling into a mold, and firing to obtain a second microchannel reactor;

weighing 1 part of androstane-3, 5-diene-17 beta-alcohol-3-acetate and 100 parts of DMF, uniformly mixing to obtain a first solution, weighing 1.2 parts of liquid bromine and 100 parts of DMF, uniformly mixing to obtain a second solution, respectively pumping the first solution and the second solution into a first microchannel reactor, keeping the temperature in the first microchannel reactor at 0 ℃, the pressure at 0.2MPa, the volume of the first microchannel reactor at 10 mu L, keeping the residence time of the first microchannel reactor at 2min, and collecting a reaction solution discharged from the first microchannel reactor after the reaction is finished;

weighing 0.5 part of sodium hydroxide and 100 parts of ethanol, mixing and stirring uniformly to obtain an ethanol solution of the sodium hydroxide, pumping a reaction solution discharged from a first microchannel reactor and the ethanol solution of the sodium hydroxide into a second microchannel reactor respectively, keeping the temperature in the microchannel reactor at 0 ℃, the pressure at 0.1MPa, the volume of the second microchannel reactor at 10 mu L, the residence time of the second microchannel reactor at 1min, and collecting the reaction solution discharged from the second microchannel reactor after the reaction is finished;

weighing 1.5 parts of acetic anhydride and 0.1 part of triethylamine, uniformly mixing, pumping the mixture and reaction liquid discharged from a second microchannel reactor into a third microchannel reactor respectively, keeping the temperature in the third microchannel reactor at 0 ℃, the pressure at 0.1MPa, the volume of the third microchannel reactor at 10 mu L, keeping the residence time of the third microchannel reactor at 1min, collecting the reaction liquid discharged from the third microchannel reactor after the reaction is finished, cleaning the reaction liquid to be neutral by using a saturated sodium bicarbonate solution, no bubble is generated, standing for layering, taking an organic layer, concentrating and drying to obtain the dehydronandrolone acetate.

Example 2

Respectively weighing 1 part of palladium nitrate, 3 parts of silver nitrate, 1 part of terephthalic acid and 200 parts of water, mixing, heating to 55 ℃ by microwave under the ultrasonic condition, stirring for 60min to obtain a precursor solution, and drying the precursor solution to be powdery.

Weighing 1 part of precursor powder, 2 parts of alumina and 0.2 part of aluminum powder, uniformly mixing, filling into a mold, and firing to obtain a first microchannel reactor;

respectively weighing 1 part of ferric chloride, 1 part of aluminum chloride and 200 parts of water, stirring for 20min under the ultrasonic condition to obtain a mixed solution, dropwise adding ammonia water into the mixed solution until white suspended matters appear in the solution, stopping dropwise adding, drying the mixed solution to obtain carrier powder, weighing 1 part of carrier powder and 3 parts of zinc oxide powder, uniformly mixing, filling into a mold, and firing to obtain a second microchannel reactor;

weighing 1 part of androstane-3, 5-diene-17 beta-alcohol-3-acetate and 100 parts of DMF, uniformly mixing to obtain a first solution, weighing 1.3 parts of liquid bromine and 100 parts of DMF, uniformly mixing to obtain a second solution, respectively pumping the first solution and the second solution into a first microchannel reactor, keeping the temperature in the first microchannel reactor at 5 ℃, the pressure at 0.3MPa, the volume of the first microchannel reactor at 10 mu L, keeping the residence time of the first microchannel reactor at 2min, and collecting a reaction solution discharged from the first microchannel reactor after the reaction is finished;

weighing 0.6 part of sodium hydroxide and 100 parts of ethanol, mixing and stirring uniformly to obtain an ethanol solution of the sodium hydroxide, pumping a reaction solution discharged from a first microchannel reactor and the ethanol solution of the sodium hydroxide into a second microchannel reactor respectively, keeping the temperature in the microchannel reactor at 5 ℃, the pressure at 0.2MPa, the volume of the second microchannel reactor at 10 mu L, the residence time of the second microchannel reactor at 1min, and collecting the reaction solution discharged from the second microchannel reactor after the reaction is finished;

weighing 1.6 parts of acetic anhydride and 0.2 part of triethylamine, uniformly mixing, pumping the mixture and reaction liquid discharged from a second microchannel reactor into a third microchannel reactor respectively, keeping the temperature in the third microchannel reactor at 5 ℃, the pressure at 0.2MPa, the volume of the third microchannel reactor at 10 mu L, keeping the residence time of the third microchannel reactor at 1min, collecting the reaction liquid discharged from the third microchannel reactor after the reaction is finished, cleaning the reaction liquid to be neutral by using a saturated sodium bicarbonate solution, no bubble is generated, standing for layering, taking an organic layer, concentrating and drying to obtain the dehydronandrolone acetate.

Example 3

Respectively weighing 1 part of palladium nitrate, 4 parts of silver nitrate, 2 parts of terephthalic acid and 500 parts of water, mixing, heating to 60 ℃ by microwave under the ultrasonic condition, stirring for 40min to obtain a precursor solution, and drying the precursor solution to be powdery.

Weighing 1 part of precursor powder, 3 parts of alumina and 0.3 part of aluminum powder, uniformly mixing, filling into a mold, and firing to obtain a first microchannel reactor;

respectively weighing 1 part of ferric chloride, 1 part of aluminum chloride and 300 parts of water, stirring for 30min under an ultrasonic condition to obtain a mixed solution, dropwise adding ammonia water into the mixed solution until white suspended matters appear in the solution, stopping dropwise adding, drying the mixed solution to obtain carrier powder, weighing 1 part of carrier powder and 3 parts of zinc oxide powder, uniformly mixing, filling into a mold, and firing to obtain a second microchannel reactor;

weighing 1 part of androstane-3, 5-diene-17 beta-alcohol-3-acetate and 100 parts of DMF, uniformly mixing to obtain a first solution, weighing 1.4 parts of liquid bromine and 100 parts of DMF, uniformly mixing to obtain a second solution, respectively pumping the first solution and the second solution into a first microchannel reactor, keeping the temperature in the first microchannel reactor at 10 ℃, the pressure at 0.2MPa, the volume of the first microchannel reactor at 10 mu L, keeping the residence time of the first microchannel reactor at 1min, and collecting a reaction solution discharged from the first microchannel reactor after the reaction is finished;

weighing 0.7 part of sodium hydroxide and 100 parts of ethanol, mixing and stirring uniformly to obtain an ethanol solution of the sodium hydroxide, pumping a reaction solution discharged from a first microchannel reactor and the ethanol solution of the sodium hydroxide into a second microchannel reactor respectively, keeping the temperature in the microchannel reactor at 10 ℃, the pressure at 0.3MPa, the volume of the second microchannel reactor at 10 mu L and the residence time of the second microchannel reactor at 1min, and collecting the reaction solution discharged from the second microchannel reactor after the reaction is finished;

weighing 1.8 parts of acetic anhydride and 0.2 part of triethylamine, uniformly mixing, pumping the mixture and reaction liquid discharged from a second microchannel reactor into a third microchannel reactor respectively, keeping the temperature in the third microchannel reactor at 10 ℃, the pressure at 0.3MPa, the volume of the third microchannel reactor at 10 mu L, keeping the residence time of the third microchannel reactor at 1min, collecting the reaction liquid discharged from the third microchannel reactor after the reaction is finished, cleaning the reaction liquid to be neutral by using a saturated sodium bicarbonate solution, no bubble is generated, standing for layering, taking an organic layer, concentrating and drying to obtain the dehydronandrolone acetate.

Comparative example 1

Weighing 1 part of androstane-3, 5-diene-17 beta-alcohol-3-acetate, adding 20 parts of DMF, mixing and stirring uniformly for later use, weighing 0.5 part of NBS and 10 parts of DMF, mixing and stirring uniformly, keeping the temperature at-5 ℃, dropwise adding the DMF solution of NBS into the DMF solution of androstane-3, 5-diene-17 beta-alcohol-3-acetate, keeping the temperature at-5 ℃, and after finishing low price, keeping the temperature at-5 ℃ for reaction for 1 hour to obtain a first solution;

adding sodium bisulfite into the first solution, heating to 20 ℃, keeping the temperature and stirring for 10min, then adding 0.3 part of lithium bromide and 0.6 part of lithium carbonate, keeping the temperature and stirring for 20min, then slowly heating to 80 ℃ within 1h, keeping the temperature of 80 ℃ and reacting for 2h, cooling the obtained product system to 20 ℃, dropwise adding an acetic acid solution, stirring and crystallizing for 10h at normal temperature, filtering, washing the filter cake with DMF and water respectively, mixing and heating the filter cake and isopropanol to 45 ℃ for dissolving, then slowly dropwise adding water into the solution, dropwise adding for 30min, cooling the solution to-5 ℃, keeping the temperature and stirring for 1h, filtering, leaching the filter cake with isopropanol and water respectively, and then vacuum drying to obtain dehydronandrolone;

feeding dehydronandrolone, dichloromethane, ammonium acetate and triethylamine into a reaction bottle according to the part ratio of 1:12:3:0.02, heating to 45 ℃, reacting for 90min, then cleaning the reaction solution with saturated sodium bicarbonate solution until the reaction solution is neutral, separating to obtain an organic layer when no bubbles are generated, concentrating and drying the organic layer to obtain dehydronandrolone acetate.

Comparative example 2

Weighing 1 part of androstane-3, 5-diene-17 beta-alcohol-3-acetate and 100 parts of DMF (dimethyl formamide), uniformly mixing to obtain a first solution, weighing 1.3 parts of liquid bromine and 100 parts of DMF, uniformly mixing to obtain a second solution, respectively pumping the first solution and the second solution into a microchannel reactor, keeping the temperature in the microchannel reactor at 5 ℃, the pressure at 0.3MPa, the volume of the microchannel reactor at 10 mu L, keeping the residence time of the microchannel reactor at 2min, and collecting a first reaction solution discharged from the microchannel reactor after the reaction is finished;

weighing 0.6 part of sodium hydroxide and 100 parts of ethanol, mixing and stirring uniformly to obtain an ethanol solution of the sodium hydroxide, pumping the first reaction liquid and the ethanol solution of the sodium hydroxide into a microchannel reactor respectively, keeping the temperature in the microchannel reactor at 5 ℃, the pressure at 0.2MPa, the volume of the microchannel reactor at 10 mu L, keeping the residence time of the microchannel reactor at 1min, and collecting a second reaction liquid discharged from the microchannel reactor after the reaction is finished;

weighing 1.6 parts of acetic anhydride and 0.2 part of triethylamine, uniformly mixing, pumping the mixture and a second reaction solution into a third microchannel reactor respectively, keeping the temperature in the microchannel reactor at 5 ℃, the pressure at 0.2MPa, the volume of the microchannel reactor at 10 mu L, keeping the residence time of the microchannel reactor at 1min, collecting the reaction solution discharged from the microchannel reactor after the reaction is finished, cleaning the reaction solution to be neutral by using a saturated sodium bicarbonate solution, avoiding bubbling, standing for layering, taking an organic layer, concentrating and drying to obtain the dehydronandrolone acetate.

Comparative example 3

Respectively weighing 1 part of palladium nitrate, 3 parts of silver nitrate, 1 part of terephthalic acid and 200 parts of water, mixing, heating to 55 ℃ by microwave under the ultrasonic condition, stirring for 60min to obtain a precursor solution, and drying the precursor solution to be powdery.

Weighing 1 part of precursor powder, 2 parts of alumina and 0.2 part of aluminum powder, uniformly mixing, filling into a mold, and firing to obtain a first microchannel reactor;

weighing 1 part of androstane-3, 5-diene-17 beta-alcohol-3-acetic ester and 100 parts of DMF, uniformly mixing to obtain a first solution, weighing 1.3 parts of liquid bromine and 100 parts of DMF, uniformly mixing to obtain a second solution, respectively pumping the first solution and the second solution into a first microchannel reactor, keeping the temperature in the first microchannel reactor at 5 ℃, the pressure at 0.3MPa, the volume of the first microchannel reactor at 10 mu L, keeping the residence time of the first microchannel reactor at 2min, and collecting a reaction solution discharged from the first microchannel reactor after the reaction is finished;

weighing 0.6 part of sodium hydroxide and 100 parts of ethanol, mixing and stirring uniformly to obtain an ethanol solution of the sodium hydroxide, pumping a reaction solution discharged from a first microchannel reactor and the ethanol solution of the sodium hydroxide into a second microchannel reactor respectively, keeping the temperature in the microchannel reactor at 5 ℃, the pressure at 0.2MPa, the volume of the second microchannel reactor at 10 mu L, the residence time of the second microchannel reactor at 1min, and collecting the reaction solution discharged from the second microchannel reactor after the reaction is finished;

weighing 1.6 parts of acetic anhydride and 0.2 part of triethylamine, uniformly mixing, pumping the mixture and reaction liquid discharged from a second microchannel reactor into a third microchannel reactor respectively, keeping the temperature in the third microchannel reactor at 5 ℃, the pressure at 0.2MPa, the volume of the third microchannel reactor at 10 mu L, keeping the residence time of the third microchannel reactor at 1min, collecting the reaction liquid discharged from the third microchannel reactor after the reaction is finished, cleaning the reaction liquid to be neutral by using a saturated sodium bicarbonate solution, no bubble is generated, standing for layering, taking an organic layer, concentrating and drying to obtain the dehydronandrolone acetate.

Comparative example 4

Respectively weighing 1 part of ferric chloride, 1 part of aluminum chloride and 200 parts of water, stirring for 20min under an ultrasonic condition to obtain a mixed solution, dropwise adding ammonia water into the mixed solution until white suspended matters appear in the solution, stopping dropwise adding, drying the mixed solution to obtain carrier powder, weighing 1 part of carrier powder and 3 parts of zinc oxide powder, uniformly mixing, filling into a mold, and firing to obtain a second microchannel reactor;

weighing 1 part of androstane-3, 5-diene-17 beta-alcohol-3-acetate and 100 parts of DMF, uniformly mixing to obtain a first solution, weighing 1.3 parts of liquid bromine and 100 parts of DMF, uniformly mixing to obtain a second solution, respectively pumping the first solution and the second solution into a first microchannel reactor, keeping the temperature in the first microchannel reactor at 5 ℃, the pressure at 0.3MPa, the volume of the first microchannel reactor at 10 mu L, keeping the residence time of the first microchannel reactor at 2min, and collecting a reaction solution discharged from the first microchannel reactor after the reaction is finished;

weighing 0.6 part of sodium hydroxide and 100 parts of ethanol, mixing and stirring uniformly to obtain an ethanol solution of the sodium hydroxide, pumping a reaction solution discharged from a first microchannel reactor and the ethanol solution of the sodium hydroxide into a second microchannel reactor respectively, keeping the temperature in the microchannel reactor at 5 ℃, the pressure at 0.2MPa, the volume of the second microchannel reactor at 10 mu L, the residence time of the second microchannel reactor at 1min, and collecting the reaction solution discharged from the second microchannel reactor after the reaction is finished;

weighing 1.6 parts of acetic anhydride and 0.2 part of triethylamine, uniformly mixing, pumping the mixture and reaction liquid discharged from a second microchannel reactor into a third microchannel reactor respectively, keeping the temperature in the third microchannel reactor at 5 ℃, the pressure at 0.2MPa, the volume of the third microchannel reactor at 10 mu L, keeping the residence time of the third microchannel reactor at 1min, collecting the reaction liquid discharged from the third microchannel reactor after the reaction is finished, cleaning the reaction liquid to be neutral by using a saturated sodium bicarbonate solution, no bubble is generated, standing for layering, taking an organic layer, concentrating and drying to obtain the dehydronandrolone acetate.

The yields of dehydronandrolone acetate prepared in the above examples and comparative examples were calculated, respectively, as follows:

grouping

Example 1

Example 2

Example 3

Comparative example 1

Comparative example 2

Comparative example 3

Comparative example 4

Yield of

93.5％

94.4％

94.7％

74.2％

71.3％

85.6％

82.4％

The dehydronandrolone acetate prepared in the above examples and comparative examples was subjected to high performance liquid chromatography, and the results of product content and impurity content were as follows:

the comparative example 1 is a preparation process in the prior art, wherein for a process of adding a bromine product, an intermediate is extremely unstable and easy to deteriorate, so that the single impurity in the product is relatively high, the total impurities are relatively high, and the process yield is obviously relatively low.

The data of comparative examples 2, 3 and 4 show that the yield of the target product is reduced and the single impurity generated in the process is increased after the conventional microchannel reactor is used for replacing the catalyst-supported microchannel reactor, so that the reaction selectivity and the reaction efficiency can be improved by using the catalyst-supported microchannel reactor.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims (9)

1. A preparation method of dehydronandrolone acetate is characterized by comprising the following steps:

s1, preparing a first microchannel reactor loaded with a first catalyst, wherein the first catalyst is palladium and silver;

s2, preparing a second microchannel reactor loaded with a second catalyst, wherein the second catalyst is iron and aluminum;

s3, mixing androstane-3, 5-diene-17 beta-alcohol-3-acetate with DMF to obtain a first solution, mixing liquid bromine with DMF to obtain a second solution, respectively pumping the first solution and the second solution into a first microchannel reactor, keeping the temperature in the first microchannel reactor at 0-10 ℃ and the pressure at 0.2-0.4MPa, and collecting reaction liquid discharged from the first microchannel reactor;

s4, preparing an ethanol solution of sodium hydroxide, pumping the reaction liquid discharged from the first microchannel reactor and the ethanol solution of sodium hydroxide into a second microchannel reactor, keeping the temperature in the microchannel reactor at 0-10 ℃ and the pressure at 0.1-0.3MPa, and collecting the reaction liquid discharged from the second microchannel reactor;

s5, pumping the reaction liquid discharged from the second microchannel reactor, the mixed solution of acetic anhydride and triethylamine into a third microchannel reactor respectively, keeping the temperature in the third microchannel reactor at 0-10 ℃ and the pressure at 0.1-0.3MPa, and collecting the reaction liquid discharged from the third microchannel reactor;

and S6, washing the reaction solution discharged from the third microchannel reactor to be neutral by using a saturated sodium bicarbonate solution, standing for layering, taking an organic layer, and concentrating the organic layer to be dry to obtain the dehydronandrolone acetate.

2. The method of preparing dehydronandrolone acetate according to claim 1, wherein the first microchannel reactor supporting the first catalyst is prepared in step S1 by a method comprising:

s11, respectively mixing a water-soluble compound of palladium, a water-soluble compound of silver, terephthalic acid and water to obtain a mixed solution, heating the mixed solution to 50-60 ℃ by microwave under the ultrasonic condition, and stirring for 30-60min to obtain a precursor solution;

s12, drying the precursor solution to be in a powder state to obtain carrier powder;

and S13, uniformly mixing the carrier powder and the binder, and firing and forming to obtain the first microchannel reactor.

3. The method of preparing dehydronandrolone acetate according to claim 2, wherein the water-soluble compound of palladium is palladium chloride or palladium nitrate, the water-soluble compound of silver is silver nitrate, the water-soluble compound of palladium: water-soluble compound of silver: terephthalic acid: the mass ratio of water is 1: (2-4): (1-2): (100-500).

4. The method of preparing dehydronandrolone acetate according to claim 2, wherein the binder is a mixture of alumina and aluminum powder, and the carrier powder: alumina: the mass ratio of the aluminum powder is 1: (1-3): (0.1-0.3).

5. The method for preparing dehydronandrolone acetate according to claim 1, wherein the mass ratio of androsta-3, 5-diene-17 β -ol-3-acetate to liquid bromine is 1: (1.2-1.4).

6. The method for preparing dehydronandrolone acetate according to claim 1, wherein the mass ratio of androsta-3, 5-diene-17 β -ol-3-acetate to sodium hydroxide is 1: (0.5-0.7).

7. The method for preparing dehydronandrolone acetate according to claim 1, wherein the mass ratio of androsta-3, 5-diene-17 β -ol-3-acetate to acetic anhydride and triethylamine is 1: (1.5-1.8): (0.1-0.2).

8. The method for preparing dehydronandrolone acetate according to claim 1, wherein the second microchannel reactor supporting the second catalyst is prepared in step S2 by a method comprising:

s21, mixing ferric chloride, aluminum chloride and water respectively, and ultrasonically stirring for 10-30min under the ultrasonic condition to obtain a mixed solution;

s22, dropwise adding ammonia water into the mixed solution obtained in the step S21 until white suspended matters appear in the solution, stopping dropwise adding, and drying the mixed solution to obtain carrier powder;

and S23, uniformly mixing the carrier powder and the binder, and firing and forming to obtain the second microchannel reactor.

9. The method for preparing dehydronandrolone acetate according to claim 8, wherein the binder is zinc oxide, and the mass ratio of the carrier powder to the zinc oxide is 1: (2-3).