CN110407902B - Method for removing 17-acetoxyl group from steroid compound - Google Patents
Method for removing 17-acetoxyl group from steroid compound Download PDFInfo
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- CN110407902B CN110407902B CN201910634250.3A CN201910634250A CN110407902B CN 110407902 B CN110407902 B CN 110407902B CN 201910634250 A CN201910634250 A CN 201910634250A CN 110407902 B CN110407902 B CN 110407902B
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- reaction
- steroid compound
- structural formula
- acetoxyl group
- boiling point
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa not substituted in position 16
Abstract
The invention discloses a method for removing 17-acetoxyl group from steroid compound, adding organic base into low boiling point solvent of halogenated hydrocarbon, aliphatic hydrocarbon, aromatic hydrocarbon, tetrahydrofuran, dioxane, etc. to react to generate steroid compound. The invention improves the yield of the reaction, and avoids using solvents with high boiling points, difficult treatment and high pollution, such as the traditional DMF, DMSO, and the like, so that the method is more suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of medicinal chemistry, and particularly relates to a method for removing 17-acetoxyl group from a steroid compound, wherein a sterene compound obtained after the 17-acetoxyl group is removed from the steroid compound is an important medical intermediate.
Background
The sterilene compound obtained after the elimination of the 17 alpha-acetoxy steroid compound is an important medical intermediate for synthesizing steroid drugs, the traditional method is to use alkali compounds such as potassium acetate to react in solvents such as DMF, DMSO and the like, and the synthesis steps are as follows:
the disadvantages of this route are: the yield is low, the used solvents are DMF, DMSO and the like, and the solvents have high boiling points, are relatively troublesome in post-treatment and have large pollution.
Disclosure of Invention
The invention aims to provide a method for removing 17-acetoxyl group from steroid compounds, which improves the original yield compared with the traditional method, avoids using traditional solvents with high boiling points, difficult treatment and large pollution such as DMF, DMSO and the like, and is more suitable for industrial production.
The invention is realized by adopting the following technical scheme:
specifically, the method for removing 17-acetoxyl group from steroid compound is characterized by comprising the following steps: adding a 17-acetoxy steroid compound with a structural formula I into a low-boiling point solvent, adding an organic base with a structural formula III, and reacting to generate a steroid compound with a structural formula II:
in the above structural formula, R1OAc, OH, carbonyl; r2H or C1-C4 alkyl.
Further, the reaction solvent in the present invention is a low boiling point solvent such as halogenated hydrocarbon, aliphatic hydrocarbon, aromatic hydrocarbon, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane or a mixture thereof, and is preferably tetrahydrofuran or dioxane.
Further, the reaction temperature in the invention is from room temperature to the reaction reflux temperature.
Further, the feeding molar ratio of the reaction substrate to the organic base is 1: 1-5, preferably 1: 2 to 3.
The invention is characterized in that:
(1) using organic bases with better catalytic effect, e.g. III (R)2＝Me)MTBD,III(R2H) TBD, etc., to improve the yield of the reaction.
(2) By selecting the reaction solvent, the solvents with high boiling points, such as DMF, DMSO and the like in the traditional method are replaced by low boiling point solvents, such as dioxane, tetrahydrofuran and the like, which are difficult to recover and have large pollution, so that the industrial production is more economic and environment-friendly.
Detailed Description
Example 1
Adding prednisone acetate 100.0mg, toluene 10mL, p-toluenesulfonic acid 90.0mg, stirring at room temperature under nitrogen protection, TLC monitoring raw material reaction, adding 50mL saturated sodium bicarbonate water-soluble solutionTerminating the reaction, extracting the organic phase with 20mL of toluene, washing with water, separating the solution, concentrating the organic layer under reduced pressure to dryness, adding 80.0mg of MTBD, 5mL of THF, heating to reflux under nitrogen protection, monitoring by TLC that the reaction of the raw materials is finished, quenching the reaction with 20mL of dilute hydrochloric acid, extracting the organic phase with 30mL of dichloromethane, separating the solution, drying the organic phase with anhydrous sodium sulfate, and concentrating the organic phase under reduced pressure to dryness to obtain the target compound II (R)1Carbonyl) 90.0mg, yield: 95.0 percent.
Example 2
Adding 100.0mg of prednisone acetate, 10mL of toluene, 90.0mg of p-toluenesulfonic acid and nitrogen protection into a dry three-neck flask in sequence, stirring at room temperature, adding 50mL of saturated sodium bicarbonate aqueous solution to stop the reaction after TLC monitoring of the raw materials finishes the reaction, extracting with 20mL of toluene, washing the organic phase with water for multiple times, separating, concentrating the organic phase under reduced pressure to dryness, adding 60.0mg of TBD (tert-butyl peroxide) and 5.0mL of dioxane, nitrogen protection, heating to reflux, quenching the reaction with 20mL of dilute hydrochloric acid after TLC monitoring of the raw materials finishes the reaction, extracting the organic phase with 30mL of dichloromethane, separating, drying the organic phase with anhydrous sodium sulfate, concentrating under reduced pressure to dryness to obtain 80.0mg of a target compound II, wherein the yield is as follows: 88.0 percent.
Claims (3)
1. A method for removing 17-acetoxyl group from steroid compounds is characterized in that: adding a 17-acetoxy steroid compound with a structural formula I into a low-boiling point solvent, adding an organic base with a structural formula III, and reacting to generate a steroid compound with a structural formula II:
in the above structural formula, R1OAc, OH, carbonyl; r2A ═ C1-C4 alkyl group;
the low boiling point solvent is halogenated hydrocarbon, aliphatic hydrocarbon, aromatic hydrocarbon, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane or a mixture thereof.
2. The method of claim 1, wherein: the reaction temperature is from room temperature to the reaction reflux temperature.
3. The method of claim 1, wherein: the feeding molar ratio of the reaction substrate I to the organic base III is 1: 1 to 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910634250.3A CN110407902B (en) | 2019-07-15 | 2019-07-15 | Method for removing 17-acetoxyl group from steroid compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910634250.3A CN110407902B (en) | 2019-07-15 | 2019-07-15 | Method for removing 17-acetoxyl group from steroid compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110407902A CN110407902A (en) | 2019-11-05 |
| CN110407902B true CN110407902B (en) | 2020-11-13 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910634250.3A Expired - Fee Related CN110407902B (en) | 2019-07-15 | 2019-07-15 | Method for removing 17-acetoxyl group from steroid compound |
Country Status (1)
| Country | Link |
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| CN (1) | CN110407902B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104262440B (en) * | 2014-09-10 | 2016-08-17 | 江西赣亮医药原料有限公司 | A kind of preparation method of 16-hydroxy prednisonlone |
| CN105061549B (en) * | 2015-08-20 | 2017-06-20 | 上海信谊百路达药业有限公司 | A kind of preparation method of budesonide |
| CN106977570A (en) * | 2017-04-18 | 2017-07-25 | 山东赛托生物科技股份有限公司 | A kind of method for synthesizing 16 dehydrogenation progesterone |
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2019
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| CN110407902A (en) | 2019-11-05 |
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