CN104017044A - Method for synthesizing 16-dehydropregnenolone by taking dehydropregnenolone acetate as raw material - Google Patents
Method for synthesizing 16-dehydropregnenolone by taking dehydropregnenolone acetate as raw material Download PDFInfo
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- CN104017044A CN104017044A CN201410268837.4A CN201410268837A CN104017044A CN 104017044 A CN104017044 A CN 104017044A CN 201410268837 A CN201410268837 A CN 201410268837A CN 104017044 A CN104017044 A CN 104017044A
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- alcohol ketone
- diene alcohol
- acetic ester
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- dehydropregnenolone
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Abstract
The invention discloses a method for synthesizing 16-dehydropregnenolone by taking dehydropregnenolone acetate as a raw material. The method comprises the following steps: dissolving dehydropregnenolone acetate by taking an aprotic solvent as a solvent, adding an aqueous solution of an inorganic base, controlling the reaction temperature to 20-30 DEG C, regulating the pH value to be neutral after the reaction is detected to be finished, raising the temperature to recover the solvent, performing atmospheric distillation and reduced pressure recovery, and adding water for filtering, wherein the filter cake is the 16-dehydropregnenolone. According to the method, protic solvents such as alcohols are avoided, hydrophilic aprotic solvents are used, a few byproducts are produced, and high-purity 16-dehydropregnenolone is obtained.
Description
Technical field
The present invention relates to the synthetic method of chemicals, particularly a kind of synthetic method of 16-gestation diene alcohol ketone
Background technology
16-gestation diene alcohol ketone is a kind of conventional medical material.At present, produce the traditional technology of 16-gestation diene alcohol ketone, to take diene alcohol ketone acetic ester as raw material, be dissolved in alcoholic solvent, add salt of wormwood or sodium hydroxide back hydrolysis to obtain, the shortcoming of this technique is exactly that side reaction is serious, and 16 two keys of diene alcohol ketone acetic ester are destroyed under the effect of alcoholic solvent and alkali, and this has affected quality product and yield.Reaction formula is as follows:
Summary of the invention
The object of this invention is to provide a kind of improved method that is obtained 16-gestation diene alcohol ketone by hydrolysis under diene alcohol ketone acetic ester alkaline condition, this inventive method yield is high, and side reaction is few.Reaction formula:
The method is as follows:
Using aprotic solvent as dissolution with solvents diene alcohol ketone acetic ester, then add wherein the aqueous solution of mineral alkali, stirring reaction, control 20 ℃ to 30 ℃ of temperature of reaction, after detection reaction completes, be adjusted to pH value to neutral, rising temperature reclamation solvent, first air distillation, rear reclaim under reduced pressure, adds water filtration, and filter cake is 16-gestation diene alcohol ketone.The present invention uses hydrophilic aprotic solvent, and by product is few, and target product purity is high.
In some embodiments, the aprotic solvent using in the inventive method for tetrahydrofuran (THF), dioxan, dimethyl sulfoxide (DMSO) (DMSO) or dimethyl formamide (DMF) wherein any.Select these aprotic solvent obviously to reduce by-product, obtain the diene alcohol ketone acetic ester hydrolyzate that purity is higher.
In some embodiments, the feed ratio of the quality of diene alcohol ketone acetic ester described in the inventive method, aprotic solvent volume and mineral alkali quality optimization is 1W:10V:0.2W.。This feed ratio has higher output ratio.
In some embodiments, the method that in the inventive method, detection reaction completes is that TLC detects the disappearance of diene alcohol ketone acetic ester raw material point.
Outstanding advantage of the present invention avoids using the protonic solvent such as alcohols in traditional technology exactly, uses hydrophilic aprotic solvent instead, and by product is few, obtains the diene alcohol ketone acetic ester hydrolyzate that purity is higher.
Accompanying drawing explanation
Fig. 1 is thin-layer chromatography (TLC detection) figure of one embodiment of the present invention.
Fig. 2 is former technique thin-layer chromatogram.
Embodiment
Embodiment 1
In reaction flask, add 200 milliliters of 20 grams of diene alcohol ketone acetic esters and tetrahydrofuran (THF)s (THF), stir 10 minutes molten clear;
To reaction flask, add 20 milliliters of 20% sodium hydroxide solutions again, be warming up to 20～30 ℃, stirring reaction insulation reaction 1 hour, reaction is TLC and is detected, Figure 1A classifies contrast diene alcohol ketone acetic ester point as, B classifies the present embodiment reaction solution point as and hardens really, and B1 is raw material diene alcohol ketone acetic ester point, and B2 is product, when detecting after diene alcohol ketone acetic ester disappears, TLC adds 10 milliliters of hydrochloric acid, it is neutral adjusting pH, and normal pressure is warming up to reflux temperature and reclaims most of solvent, and vacuum rotary steam reclaims residual solvent; And backward revolve to steam in residuum add 200 milliliters, water, filter, with 100 ml water washing leaching cakes, dry to obtain 18 grams of pregnant diene alcohol ketones of 16-, yield 90%.
Reaction formula is as follows:
By former technique, take diene alcohol ketone acetic ester as raw material, be dissolved in alcoholic solvent, add salt of wormwood or sodium hydroxide back hydrolysis to obtain 16-gestation diene alcohol ketone.
In reaction, be TLC and detect to obtain Fig. 2, C classifies as contrast diene alcohol ketone acetic ester point, and D classifies reaction solution point as and hardens really, and D1 is raw material diene alcohol ketone acetic ester, and D2 is 16-gestation diene alcohol ketone, and D3 and D4 are by product.
By Fig. 1 and Fig. 2, can find out that novel process product is pure especially, does not have by product.And former technique has obvious by product to produce.
Embodiment 2
In reaction flask, add 100 milliliters of 10 grams of DMFs of diene alcohol ketone acetic ester (DMF), stir 10 minutes molten clear;
Add 10 milliliters of 20% sodium hydroxide solutions, be warming up to 20～30 ℃, insulation reaction 1 hour, TLC detects after diene alcohol ketone acetic ester disappears and adds 5 milliliters of hydrochloric acid, some plate figure have no by-product object point identical with Fig. 1.It is neutral adjusting pH, the most of solvent of normal pressure rising temperature reclamation, reclaim under reduced pressure residual solvent; Then add 200 milliliters, water, filter, with 100 ml water washing leaching cakes, dry to obtain 8.5 grams of pregnant diene alcohol ketones of 16-.Yield 91%.
Embodiment 3
In reaction flask, add 500 milliliters of 50 grams of diene alcohol ketone acetic esters and dioxan, stir molten clear;
Add 50 milliliters of 20% sodium hydroxide solutions, room temperature reaction 3 hours, TLC detects diene alcohol ketone acetic ester and disappears, point plate figure have no by-product object point identical with Fig. 1, adds 25 milliliters of hydrochloric acid, and it is neutral adjusting pH, the most of solvent of normal pressure rising temperature reclamation, reclaim under reduced pressure residual solvent; Then add 400 milliliters, water, filter, with 100 ml water washing leaching cakes, dry to obtain 46 grams of pregnant diene alcohol ketones of 16-.Yield 89%.
Embodiment 4
In reaction flask, add 50 grams of diene alcohol ketone acetic esters, 500 milliliters of tetrahydrofuran (THF)s (THF), stir molten clear;
Add 50 milliliters of 20% sodium hydroxide solutions, room temperature reaction 3 hours, TLC detects diene alcohol ketone acetic ester and disappears, point plate figure have no by-product object point identical with Fig. 1, add 25 milliliters of hydrochloric acid to adjust pH for neutral, the most of solvent of normal pressure rising temperature reclamation, reclaim under reduced pressure residual solvent; Then add 500 milliliters, water, filter, with 100 ml water washing leaching cakes, dry to obtain 45 grams of pregnant diene alcohol ketones of 16-.Yield 93%.
Embodiment 5
In reaction flask, add 200 grams of diene alcohol ketone acetic esters, 2000 milliliters of tetrahydrofuran (THF)s (THF), stir molten clear;
Add 200 milliliters of 20% sodium hydroxide solutions, room temperature reaction 3 hours, TLC detects diene alcohol ketone acetic ester and disappears, point plate figure have no by-product object point identical with Fig. 1, add 100 milliliters of hydrochloric acid to adjust pH for neutral, the most of solvent of normal pressure rising temperature reclamation, reclaim under reduced pressure residual solvent; Then add 2000 milliliters, water, filter, with 1000 ml water washing leaching cakes, dry to obtain 185 grams of pregnant diene alcohol ketones of 16-.Yield 92%
Embodiment 6
In reaction flask, add 200 grams of diene alcohol ketone acetic esters, 2000 milliliters of tetrahydrofuran (THF)s (THF), stir molten clear;
Add 200 milliliters of 20% potassium hydroxide solutions, room temperature reaction 3 hours, TLC detects diene alcohol ketone acetic ester and disappears, point plate figure have no by-product object point identical with Fig. 1, add 100 milliliters of hydrochloric acid to adjust pH for neutral, the most of solvent of normal pressure rising temperature reclamation, reclaim under reduced pressure residual solvent; Then add 2000 milliliters, water, filter, with 1000 ml water washing leaching cakes, dry to obtain 183 grams of pregnant diene alcohol ketones of 16-.Yield 93%.
Embodiment 7
In reaction flask, add 200 grams of diene alcohol ketone acetic esters, 2000 milliliters of dimethyl sulfoxide (DMSO) (DMSO), stir molten clear;
Add 200 milliliters of 20% potassium hydroxide solutions, room temperature reaction 3 hours, TLC detects diene alcohol ketone acetic ester and disappears, point plate figure have no by-product object point identical with Fig. 1, add 100 milliliters of hydrochloric acid to adjust pH for neutral, the most of solvent of normal pressure rising temperature reclamation, reclaim under reduced pressure residual solvent; Then add 2000 milliliters, water, filter, with 1000 ml water washing leaching cakes, dry to obtain 179 grams of pregnant diene alcohol ketones of 16-.Yield 89%.
Claims (4)
1. the method that the diketene acetic ester of take is the synthetic 16-gestation of raw material diene alcohol ketone, is characterized in that comprising following processing step:
Diene alcohol ketone acetic ester is dissolved in aprotic solvent, then add wherein inorganic base aqueous solution, control 20 ℃ to 30 ℃ of temperature of reaction, after completing, detection reaction is adjusted to pH value to neutral, rising temperature reclamation solvent, first air distillation, rear reclaim under reduced pressure, add water filtration, filter cake is 16-gestation diene alcohol ketone.
2. according to claim 1ly take diketene acetic ester and be to it is characterized in that the method for the synthetic 16-gestation of raw material diene alcohol ketone: described aprotic solvent be tetrahydrofuran (THF), dioxan, DMSO or DMF wherein any.
3. according to claim 2ly take diketene acetic ester and be to it is characterized in that the method for the synthetic 16-gestation of raw material diene alcohol ketone: the feed ratio of the quality of described diene alcohol ketone acetic ester, aprotic solvent volume and mineral alkali quality optimization is 1:10:0.2.
4. according to claim 2ly take diketene acetic ester and be to it is characterized in that the method for the synthetic 16-gestation of raw material diene alcohol ketone: the method that described detection reaction completes is that TLC detects the disappearance of diene alcohol ketone acetic ester raw material point.
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| CN201410268837.4A CN104017044B (en) | 2014-06-16 | 2014-06-16 | The method being Material synthesis 16-gestation diene alcohol ketone with diketene acetate |
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| CN201410268837.4A CN104017044B (en) | 2014-06-16 | 2014-06-16 | The method being Material synthesis 16-gestation diene alcohol ketone with diketene acetate |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475494A (en) * | 2003-07-16 | 2004-02-18 | 中国科学院上海有机化学研究所 | Cleaning production technique of 16-dehydro pregnenetrolone and its same kind compound |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475494A (en) * | 2003-07-16 | 2004-02-18 | 中国科学院上海有机化学研究所 | Cleaning production technique of 16-dehydro pregnenetrolone and its same kind compound |
Non-Patent Citations (2)
| Title |
|---|
| BAPURAO B. SHINGATE ET AL.: "Stereoselective syntheses of unnatural steroidal C(20R) aldehydes by ionic hydrogenation of C-20 tertiary alcohols", 《TETRAHEDRON LETTERS》, vol. 47, 9 November 2006 (2006-11-09), pages 9343 - 9347 * |
| HONGQI LI ET AL.: "Synthesis and characterization of new phenyl esters derived from 16-dehydropregnenolone acetate (16-DPA)", 《RES CHEM INTERMED》, vol. 39, 7 November 2012 (2012-11-07), pages 3887 - 3893 * |
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