A method for preparing an arnecrodac silyl ether of acetate

Abstract

This invention belongs to the field of pharmaceutical and environmental chemistry, and specifically relates to a method for preparing anacocetate silyl ether. The method for preparing anacocetate silyl ether provided by this invention includes the following steps: (1) 9-hydroxyl elimination reaction, (2) quenching reaction, (3) pH adjustment, (4) dehydration treatment, (5) 17-hydroxyl silyl ether reaction, (6) water washing and layering, (7) concentration and crystallization, (8) solid-liquid separation, and (9) drying. The preparation method provided by this invention achieves a one-pot preparation of anacocetate silyl ether, with a product purity of over 97.5%, isomer content below 0.5%, and molar yield of over 93.4%. This invention features high yield, low pollution, simple and safe operation, and low cost. Furthermore, the preparation method is stable and easily scalable for large-scale industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical and environmental chemicals, and in particular relates to a method for preparing an anocorta silyl ether acetate compound. Background Technology

[0002] Arnechotha acetate silyl ether is a key intermediate in the synthesis of anechotha acetate and hydrocortisone, with the molecular formula C. 23 H 32 ClNO2Si, with a molecular weight of 418.05, is a white or off-white crystalline powder that decomposes under acidic, alkaline, and high-temperature conditions. The structural formula of anecoxalool acetate silyl ether is as follows:

[0003]

[0004] The synthesis of anecoxetine acetate silyl ethers begins with anecoxetine acetate hydroxyl derivative, proceeding via a 9-hydroxyl elimination reaction and a 17-hydroxyl silyl etherification reaction. The specific reaction route is as follows:

[0005]

[0006] During the synthesis of anechotha acetate cyano compounds, isomers are produced as a byproduct, and corresponding derivatives are generated in subsequent reactions. The derivatization route of anechotha acetate cyano compounds isomers is as follows:

[0007]

[0008] The synthesis of anecoxalool acetate silyl ethers in the prior art mainly suffers from the following problems:

[0009] (1) The drying time of cyano acetate is more than 72 hours, and the production cycle is long. During the drying process, cyano acetate will degrade, which will affect the quality and yield of cyano acetate.

[0010] (2) During the synthesis of cyano acetate, about 3% to 5% of isomer impurities are produced as by-products. In the finished product of cyano acetate, the size of isomer impurities is about 2%, which cannot meet the production requirements of cyano acetate. To solve this impurity problem, further purification is required, which reduces the process yield.

[0011] (3) The molar yield of synthesizing anabolic ether acetate from anabolic hydroxyl acetate using the “stepwise method” is about 88%, which is at a low level and the process cost is high.

[0012] Therefore, it is necessary to provide a method for preparing anacoctasilyl acetate that can effectively improve the yield and purity of the obtained anacoctasilyl acetate product and reduce the content of isomers. Summary of the Invention

[0013] To address the problems existing in the prior art, the present invention aims to provide a method for preparing anhydrous acetate silyl ether. The method provided by the present invention achieves a one-pot preparation of anhydrous acetate silyl ether, avoiding the centrifugation and drying steps of anhydrous acetate cyano in conventional processes. This shortens the production cycle, reduces labor intensity, avoids material loss, and solves the main problems existing in the original process technology. The method provided by the present invention effectively improves the yield and purity of the obtained anhydrous acetate silyl ether and reduces the isomer content in the finished product.

[0014] The technical solution of this invention is:

[0015] A method for preparing an anocorta silyl ether acetate includes the following steps:

[0016] Step (1), 9-hydroxyl elimination reaction: Add the hydroxyl group of acetic acid to the reaction solvent, control the temperature at -20 to -30℃, stir until dissolved, and then transfer it to the elimination agent. After the transfer is complete, control the temperature at -10 to 0℃ and continue the reaction for 1 to 5 hours. After the reaction is complete, the cyano acetate reaction solution is obtained, and proceed to the next step.

[0017] Step (2), Quenching reaction: Add water to the cyanide acetate reaction solution obtained in step (1), stir for 0.5 h, let stand for 0.5 h, separate into layers, discard the aqueous phase, and obtain organic phase I to proceed to the next step;

[0018] Step (3), pH adjustment: Add 5% sodium carbonate aqueous solution to organic phase I obtained in step (2) to adjust the pH to 7-8, stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase II to proceed to the next step;

[0019] Step (4), Dehydration treatment: Add anhydrous sodium sulfate to the organic phase II obtained in step (3), stir for 2-8 hours, separate solid and liquid, treat the solid material with conventional technical means to recover anhydrous sodium sulfate, and the liquid material enters the next step;

[0020] Step (5), 17-hydroxy silyl ether reaction: Add imidazole to the liquid material obtained in step (4), control the temperature at 10-20℃, add chloromethyldimethylchlorosilane, after the addition is complete, control the temperature at 10-20℃ and continue the reaction for 1-5 hours. After the reaction is complete, the reaction solution of acetic acid anocorta silyl ether is obtained, and proceed to the next step.

[0021] Step (6), water washing and layering: add water to the reaction solution of acetic acid arnechoic acid silyl ether obtained in step (5), stir for 0.5 h, let stand for 0.5 h, layering, discard the aqueous phase, and obtain organic phase III to proceed to the next step;

[0022] Step (7), Concentration and Crystallization: The organic phase III obtained in step (6) is concentrated, and gaseous material and solid-liquid mixture are obtained during the concentration process;

[0023] The gaseous material is condensed and recovered to obtain the reaction solvent. The reaction solvent enters the solvent recovery workshop and is recovered by conventional distillation. It can then be recycled in this process.

[0024] The solid-liquid mixture is cooled to -10 to 0°C and kept at that temperature for 1 to 5 hours before proceeding to the next step.

[0025] Step (8), solid-liquid separation: the material obtained in step (7) is separated into solid and liquid, the mother liquor is centrally recycled, and the solid material enters the next step;

[0026] Step (9), Drying: The solid material obtained in step (8) is placed at 40-60℃ and dried until the weight loss during drying is less than 0.5%, to obtain the finished product of acetic acid silyl ether.

[0027] Further, in step (1), the reaction solvent is at least one of dichloromethane, chloroform or tetrahydrofuran; the mass ratio of the acetic acid anocetate hydroxyl compound to the reaction solvent is 1:3 to 8.

[0028] Further, in step (1), the eliminator is at least one of phosphorus oxychloride, concentrated sulfuric acid, or chlorosulfonic acid; the molar ratio of the acetic acid anocetate hydroxyl compound to the eliminator is 1:1 to 3.

[0029] Furthermore, by adding a specific proportion of arnechoic acid hydroxyl compound, reaction solvent and eliminator in step (1) of the present invention, the molar yield of the final product can be effectively increased, the reaction rate can be increased and the content of isomers in the product can be reduced.

[0030] Furthermore, the mass ratio of the amount of water added in step (2) to the amount of hydroxyl acetate added in step (1) is 0.5 to 2.0:1.

[0031] Furthermore, the mass ratio of the amount of anhydrous sodium sulfate added in step (4) to the amount of hydroxyl acetate added in step (1) is 0.1 to 1.0:1. Adding anhydrous sodium sulfate within this range ensures sufficient water removal during the dehydration process in step (4), thus guaranteeing the anhydrous conditions required for the silane etherification reaction. On the other hand, it avoids the generation of excessive solid materials, thus preventing material waste.

[0032] Furthermore, the mass ratio of the amount of imidazole added in step (5) to the amount of anocetate hydroxyl acetate added in step (1) is 0.1 to 1.0:1.

[0033] Furthermore, the mass ratio of the amount of chloromethyldimethylchlorosilane added in step (5) to the amount of acetic acid hydroxyl compound added in step (1) is 0.5 to 2.0:1.

[0034] Furthermore, adding imidazole and chloromethyldimethylchlorosilane within this ratio range in step (5) can effectively reduce production costs while ensuring the reaction process is fully complete.

[0035] Furthermore, the mass ratio of the amount of water added in step (6) to the amount of hydroxyl acetate added in step (1) is 0.5 to 2.0:1.

[0036] Further, the ratio of the concentrated solid-liquid mixture in step (7) to the amount of anabolic hydroxy acetate added in step (1) is 1.0 to 5.0:1, wherein the solid-liquid mixture is in volume (mL) and the anabolic hydroxy acetate is in weight (g).

[0037] Compared with the prior art, the preparation method of anecoxal silyl ether acetate provided by the present invention has the following advantages:

[0038] (1) This invention employs a technique of transferring the clear solution of anabolic hydroxyl acetate into an eliminator. During the reaction, the concentration of the eliminator is maintained at a high level, which allows the isomer content of anabolic hydroxyl acetate to be controlled below 0.5%, providing a high-quality raw material for further preparation of anabolic hydroxyl acetate. Using the anabolic hydroxyl acetate obtained by this invention, the preparation of anabolic hydroxyl acetate does not require purification, and the isomer content of the finished anabolic hydroxyl acetate can be controlled below 0.15%. This process technology reduces labor intensity, simplifies operation, avoids material loss, and improves process yield.

[0039] (2) This invention employs liquid-liquid separation and adsorption dehydration techniques to achieve a one-pot preparation of anabolic silyl ether acetate. This process avoids the centrifugation and drying steps of anabolic cyanate acetate, shortens the production cycle, reduces labor intensity, avoids material loss, and solves the main problems existing in the original process technology.

[0040] (3) The process technology provided by the present invention is used to prepare anabolic ether acetate from anabolic hydroxyl acetate. The product purity is above 97.5%, the isomer content is below 0.5%, and the molar yield is above 93.4%, which is higher than the molar yield of the original process (around 88%). Attached Figure Description

[0041] Figure 1 This is a flowchart illustrating the preparation method of the anechodine silyl ether compound in this invention. Detailed Implementation

[0042] The present invention will be further described below through specific embodiments, but this is not a limitation of the present invention. Those skilled in the art can make various modifications or improvements based on the basic idea of ​​the present invention, but as long as they do not depart from the basic idea of ​​the present invention, they are all within the protection scope of the present invention.

[0043] Unless otherwise specified, the reagents used in the following examples and comparative examples are conventional reagents and can be purchased from conventional reagent manufacturers and distributors; the methods used are all prior art unless otherwise specified.

[0044] Example 1: A method for preparing an arnechoica silyl ether compound.

[0045] The method for preparing the aforementioned anocorta silyl ether acetate includes the following steps:

[0046] Step (1), 9-hydroxyl elimination reaction: Add 100g of anocorta acetate hydroxy compound to 800g of tetrahydrofuran, control the temperature at -20℃, stir until dissolved, and then transfer to 46.5g of phosphorus oxychloride. After the transfer is complete, control the temperature at -10℃ and continue the reaction for 5h. After the reaction is complete, the anocorta acetate cyano compound reaction solution is obtained, and proceed to the next step.

[0047] Step (2), Quenching reaction: Add 50g of water to the cyano acetate reaction solution obtained in step (1), stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase I to proceed to the next step;

[0048] Step (3) Adjusting pH value: Add 5% sodium carbonate aqueous solution to organic phase I obtained in step (2), adjust pH value to 7, stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase II to proceed to the next step;

[0049] Step (4), Dehydration treatment: Add 10g of anhydrous sodium sulfate to the organic phase II obtained in step (3), stir for 8h, separate solid and liquid, treat the solid material with conventional technical means to recover anhydrous sodium sulfate, and the liquid material enters the next step;

[0050] Step (5), 17-hydroxy silyl ether reaction: Add 10g imidazole to the liquid material obtained in step (4), control the temperature at 20℃, add 50g chloromethyldimethylchlorosilane, after the addition is complete, continue the reaction at 20℃ for 1h, after the reaction is complete, the reaction solution of acetic acid anocorta silyl ether is obtained, and proceed to the next step.

[0051] Step (6), water washing and layering: Add 50g of water to the reaction solution of acetic acid arnecotha ether obtained in step (5), stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase III to proceed to the next step;

[0052] Step (7), Concentration and Crystallization: The organic phase III obtained in step (6) is concentrated. During the concentration process, a gaseous material and a solid-liquid mixture are obtained. The gaseous material is condensed to obtain tetrahydrofuran. The tetrahydrofuran obtained by condensation can be recycled in this process after being recovered by conventional distillation.

[0053] The volume of the solid-liquid mixture obtained is 500 mL. The mixture is cooled to 0°C and kept at that temperature for 5 hours before proceeding to the next step.

[0054] Step (8), solid-liquid separation: the material obtained in step (7) is separated into solid and liquid, the mother liquor is centrally recycled, and the solid material enters the next step;

[0055] Step (9), Drying: The solid material obtained in step (8) is placed at 60°C for drying, and the limit of drying weight loss is 0.35%, to obtain 118.5g of anechodine silyl ether acetate product.

[0056] Example 2: A method for preparing an arnechoica silyl ether compound.

[0057] The method for preparing the aforementioned anocorta silyl ether acetate includes the following steps:

[0058] Step (1), 9-hydroxyl elimination reaction: Add 100g of anocorta acetate hydroxy compound to 300g of dichloromethane, control the temperature at -25℃, stir until dissolved, and then transfer to 238g of 98% concentrated sulfuric acid. After the transfer is complete, continue the reaction at 5℃ for 1h. After the reaction is complete, the anocorta acetate cyano compound reaction solution is obtained, and proceed to the next step.

[0059] Step (2), Quenching reaction: Add 100g of water to the cyano acetate reaction solution obtained in step (1), stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase I to proceed to the next step;

[0060] Step (3) Adjusting pH value: Add 5% sodium carbonate aqueous solution to organic phase I obtained in step (2), adjust pH value to 8, stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase II to proceed to the next step;

[0061] Step (4), Dehydration treatment: Add 100g of anhydrous sodium sulfate to the organic phase I obtained in step (3), stir for 2h, separate solid and liquid, treat the solid material with conventional technical means to recover anhydrous sodium sulfate, and the liquid material enters the next step;

[0062] Step (5), 17-hydroxy silyl ether reaction: Add 100g imidazole to the liquid material obtained in step (4), control the temperature at 10℃, add 200g chloromethyldimethylchlorosilane, after the addition is complete, control the temperature at 10℃ and continue the reaction for 1h. After the reaction is complete, the reaction solution of acetic acid anocorta silyl ether is obtained, and proceed to the next step.

[0063] Step (6), water washing and layering: Add 200g of water to the reaction solution of acetic acid arnecotha ether obtained in step (5), stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase III to proceed to the next step;

[0064] Step (7), Concentration and Crystallization: The organic phase concentration III obtained in step (6) is concentrated. During the concentration process, a gaseous material and a solid-liquid mixture are obtained. The gaseous material is condensed to obtain dichloromethane. The dichloromethane obtained by condensation is recovered by conventional distillation and can be recycled in this process.

[0065] The volume of the solid-liquid mixture obtained is 100 mL. The mixture is cooled to -10°C and kept at that temperature for 1 hour before proceeding to the next step.

[0066] Step (8), solid-liquid separation: the material obtained in step (7) is separated into solid and liquid, the mother liquor is centrally recycled, and the solid material enters the next step;

[0067] Step (9), Drying: The solid material obtained in step (8) is placed at 40°C for drying, and the limit of drying weight loss is 0.15%, to obtain 119.0g of anechodine silyl ether acetate product.

[0068] Example 3: A method for preparing an arnechoica silyl ether compound.

[0069] The method for preparing the aforementioned anocorta silyl ether acetate includes the following steps:

[0070] Step (1), 9-hydroxyl elimination reaction: Add 100g of acetic acid hydroxyl compound to 500g of chloroform, control the temperature at -30℃, stir until dissolved, and then slowly transfer to 70.7g of chlorosulfonic acid. After the transfer is complete, control the temperature at 0℃ and continue the reaction for 3h. After the reaction is complete, the acetic acid cyano compound reaction solution is obtained, and proceed to the next step.

[0071] Step (2), Quenching reaction: Add 200g of water to the cyano acetate reaction solution obtained in step (1), stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase I to proceed to the next step;

[0072] Step (3) Adjusting pH: Add 5% sodium carbonate aqueous solution to organic phase I obtained in step (2), adjust pH to 7.5, stir for 0.5 h, let stand for 0.5 h, separate into layers, discard the aqueous phase, and obtain organic phase II to proceed to the next step;

[0073] Step (4), Dehydration treatment: Add 50g of anhydrous sodium sulfate to the organic phase II obtained in step (3), stir for 5h, separate solid and liquid, treat the solid material with conventional technical means to recover anhydrous sodium sulfate, and the liquid material enters the next step;

[0074] Step (5), 17-hydroxy silyl ether reaction: Add 50g imidazole to the liquid material obtained in step (4), control the temperature at 15℃, add 120g chloromethyldimethylchlorosilane, after the addition is complete, continue the reaction at 15℃ for 3h, after the reaction is complete, the reaction solution of acetic acid anocorta silyl ether is obtained, and proceed to the next step.

[0075] Step (6), water washing and layering: Add 150g of water to the reaction solution of acetic acid arnecotha ether obtained in step (5), stir for 0.5h, let stand for 0.5h, separate into layers, discard the aqueous phase, and obtain organic phase III to proceed to the next step;

[0076] Step (7), Concentration and Crystallization: The organic phase concentration III obtained in step (6) is concentrated. During the concentration process, a gaseous material and a solid-liquid mixture are obtained. The gaseous material is condensed to obtain chloroform. The chloroform obtained by condensation is recovered by conventional distillation and can be recycled in this process.

[0077] The volume of the solid-liquid mixture obtained is 200 mL. The mixture is cooled to -5°C and kept at that temperature for 3 hours before proceeding to the next step.

[0078] Step (8), solid-liquid separation: the material obtained in step (7) is separated into solid and liquid, the mother liquor is centrally recycled, and the solid material enters the next step;

[0079] Step (9), Drying: The solid material obtained in step (8) is placed at 50°C and dried. The limit of drying weight loss is 0.45%, resulting in 118.7g of anechodine silyl ether acetate product.

[0080] Comparative Example 1: A method for preparing an arnechoica silyl ether compound of acetate

[0081] The conventional preparation process for the aforementioned anecoxetine silyl ether acetate includes the following steps:

[0082] Step (1), 9-hydroxyl elimination reaction: 100g of anocorta acetate hydroxy compound was added to 800g of tetrahydrofuran, and the mixture was stirred and dissolved at -20℃. Then, 46.5g of phosphorus oxychloride was added, and the mixture was stirred and dissolved at -10℃ for 5 hours. After the reaction was completed, anocorta acetate cyanide reaction solution was obtained, and the next step was carried out.

[0083] Step (2), Quenching reaction: Add 500g of water to the reaction solution of acetic acid cyanide obtained in step (1), cool to 20℃, and crystallize for 2h; obtain solid material to proceed to the next step;

[0084] Step (3), Drying: The solid material obtained in step (2) is placed at 60°C for drying, and the limit of drying weight loss is 0.35%, to obtain 120.5g of anechodine silyl ether acetate product.

[0085] Comparative Example 2: A method for preparing an arnechoica silyl ether compound of acetate

[0086] Compared with Example 2, the difference in Comparative Example 2 is that the specific process of the 9-hydroxyl elimination reaction in step (1) is as follows: 100g of anocorta acetate hydroxy compound is added to 300g of dichloromethane, the temperature is controlled at -10℃, and the mixture is stirred until dissolved. Then, it is transferred to 238g of concentrated sulfuric acid with a mass fraction of 98%. After the transfer is completed, the temperature is controlled at 5℃ and the reaction continues for 1 hour. After the reaction is completed, anocorta acetate cyano compound reaction solution is obtained, and the next step is carried out.

[0087] The process parameters and operations for the other steps are the same as in Example 2.

[0088] Experimental Example 1: Quality Index Detection of the Arnechothecetin Acetate Silyl Ether Prepared by the Invention

[0089] The molar yield (%), purity (%), and isomer content (%) of the anecoxat silyl ether acetate products prepared in Examples 1-3 and Comparative Examples 1-2 of this invention were tested respectively.

[0090] Purity and isomer content were detected using high-performance liquid chromatography (HPLC). The detection conditions are shown in Table 1, and the detection results are shown in Table 2.

[0091] Table 1

[0092] chromatographic column Agilent SB C18, 4.6mmx250mm, 5um mobile phase Acetyl-water (85:15) Injection volume 20μL Flow rate 1.0 mL / min Column temperature 40℃ Detection wavelength 242nm Regarding the duration of material operation 40min Content running time 25min

[0093] Table 2

[0094] Group Molar yield (%) purity(%) Isomer content (%) Example 1 93.4 97.5 0.45 Example 2 93.8 98.3 0.43 Example 3 93.5 97.8 0.48 Comparative Example 1 88.2 96.2 2.10 Comparative Example 2 90.5 97.2 1.20

[0095] As shown in Table 2, the molar yield of anocetate silyl ether acetate prepared by the methods provided in Examples 1-3 of this invention is above 93.4%, the product purity is above 97.5%, and the isomer content is below 0.5%. Example 2 shows the best results and is the optimal embodiment of this invention. It can be seen that the one-pot process for preparing anocetate silyl ether acetate provided by this invention can effectively improve the molar yield and purity of the obtained anocetate silyl ether acetate, and reduce its isomer content; it also shortens the production cycle, reduces labor intensity, and improves process efficiency, solving the main problems existing in the original process technology.

[0096] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A method for preparing an anocorta silyl ether acetate compound, characterized in that, Includes the following steps: Step (1), 9-position hydroxyl elimination reaction: Add the hydroxyl group of anocetate acetate to the reaction solvent, control the temperature at -20~-30℃, stir until dissolved, and then transfer it to the elimination agent. After the transfer is complete, control the temperature at -10~0℃ and continue the reaction for 1~5 h. After the reaction is complete, the cyano acetate reaction solution is obtained, and proceed to the next step. Step (2), Quenching reaction: Add water to the cyanide acetate reaction solution obtained in step (1), stir for 0.5 h, let stand for 0.5 h, separate into layers, discard the aqueous phase, and obtain organic phase I to proceed to the next step; Step (3) Adjusting pH value: Add 5% sodium carbonate aqueous solution to organic phase I obtained in step (2) to adjust the pH value to 7~8, stir for 0.5 h, let stand for 0.5 h, separate into layers, discard the aqueous phase, and obtain organic phase II to proceed to the next step; Step (4), Dehydration treatment: Add anhydrous sodium sulfate to the organic phase II obtained in step (3), stir for 2-8 h, separate solid and liquid, the solid material is recycled to obtain anhydrous sodium sulfate, and the liquid material enters the next step; Step (5), 17-hydroxy silyl ether reaction: Add imidazole to the liquid material obtained in step (4), control the temperature at 10~20℃, add chloromethyldimethylchlorosilane, after the addition is complete, control the temperature at 10~20℃ and continue the reaction for 1~5 h, after the reaction is complete, the reaction solution of acetic acid anocorta silyl ether is obtained, and proceed to the next step; Step (6), water washing and layering: add water to the reaction solution of acetic acid arnecotha ether obtained in step (5), stir for 0.5 h, let stand for 0.5 h, layering, discard the aqueous phase, and obtain organic phase III to proceed to the next step; Step (7), Concentration and Crystallization: The organic phase III obtained in step (6) is concentrated, and gaseous material and solid-liquid mixture are obtained during the concentration process; the gaseous material is condensed and then recycled, and the solid-liquid mixture is cooled to -10~0℃ and kept at the temperature for 1~5 h before proceeding to the next step. Step (8), solid-liquid separation: the material obtained in step (7) is separated into solid and liquid, the mother liquor is centrally recycled, and the solid material enters the next step; Step (9), Drying: The solid material obtained in step (8) is placed at 40~60℃ and dried until the weight loss during drying is less than 0.5% to obtain the finished product of acetic acid silyl ether. The structural formula of the hydroxyl acetate is as follows: The structural formula of the anechotha acetate cyano compound is as follows: The structural formula of the anechostatin acetate silyl ether compound is as follows: ； In step (1), the reaction solvent is at least one of dichloromethane, chloroform, or tetrahydrofuran; the mass ratio of the acetic acid hydroxyl group to the reaction solvent is 1:3~8; In step (1), the eliminator is at least one of phosphorus oxychloride, concentrated sulfuric acid, or chlorosulfonic acid; the molar ratio of the acetic acid anocorticotropic hydroxy compound to the eliminator is 1:1~3; The mass ratio of the amount of anhydrous sodium sulfate added in step (4) to the amount of hydroxyl acetate added in step (1) is 0.1~1.0:1; The mass ratio of the amount of imidazole added in step (5) to the amount of hydroxyl acetate added in step (1) is 0.1~1.0:

1.

2. The method for preparing anabolic silyl ether acetate according to claim 1, characterized in that, The mass ratio of the amount of water added in step (2) to the amount of acetic acid hydroxyl compound added in step (1) is 0.5~2.0:

1.

3. The method for preparing the anecoxetine silyl ether compound according to claim 1, characterized in that, The mass ratio of the amount of chloromethyldimethylchlorosilane added in step (5) to the amount of acetic acid hydroxyl compound added in step (1) is 0.5~2.0:

1.

4. The method for preparing anabolic silyl ether acetate according to claim 1, characterized in that, The mass ratio of the amount of water added in step (6) to the amount of hydroxy acetate added in step (1) is 0.5~2.0:

1.

5. The method for preparing the anecoxetine silyl ether compound according to claim 1, characterized in that, The ratio of the concentrated solid-liquid mixture in step (7) to the amount of arnechoic acid added in step (1) is 1.0~5.0:1, wherein the solid-liquid mixture is in volume (mL) and the arnechoic acid is in weight (g).

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