AU2018100820A4 - Pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method - Google Patents
Pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method Download PDFInfo
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- AU2018100820A4 AU2018100820A4 AU2018100820A AU2018100820A AU2018100820A4 AU 2018100820 A4 AU2018100820 A4 AU 2018100820A4 AU 2018100820 A AU2018100820 A AU 2018100820A AU 2018100820 A AU2018100820 A AU 2018100820A AU 2018100820 A4 AU2018100820 A4 AU 2018100820A4
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- androstane
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
- C07C51/31—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation of cyclic compounds with ring-splitting
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method Abstract The present invention discloses pharmaceutical intermediates androstane-2,3 -break-i 7-ketone-2, 3-dicarboxylic acid synthesis method, comprises the following steps: androstane-1,4-dichloro-2p,3p-glycol-17 ketone, diethylbenzene solution were added to the reaction vessel, raised the temperature of the solution, 10 controlled the stirring speed, added potassium nitrate solution, reacted; continued to add antimony trioxide anhydride, glycerol ester solution, raised the temperature of the solution, reacted, filter, diluted with potassium chloride solution, added oxalic acid solution to adjust pH, lay up,reduced the temperature of the solution, washed with the sodium sulfate solution, washed with the 2-cycloheptanone solution, re-crystallized in 15 the dimethyl disulfide solution, dehydrated with dehydration, got the finished product androstane-2,3 -break-17-ketone-2, 3-dicarboxylic acid.
Description
The present invention discloses pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method, comprises the following steps: androstane-l,4-dichloro-2p,3P-glycol-17 ketone, diethylbenzene solution were added to the reaction vessel, raised the temperature of the solution, controlled the stirring speed, added potassium nitrate solution, reacted; continued to add antimony trioxide anhydride, glycerol ester solution, raised the temperature of the solution, reacted, filter, diluted with potassium chloride solution, added oxalic acid solution to adjust pH, lay up,reduced the temperature of the solution, washed with the sodium sulfate solution, washed with the 2-cycloheptanone solution, re-crystallized in the dimethyl disulfide solution, dehydrated with dehydration, got the finished product androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid.
2018100820 19 Jun 2018
Pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method
FIELD OF THE INVENTION
The present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method.
GENERAL BACKGROUND
Androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid is mainly used for the synthesis of propargyl ester poisoning drugs, as a contraceptive, it has anti implantation effect and no progesterone activity. Its estrogenic activity is 1/36 of ethinylestradiol. Small doses have synergistic effects with progesterone, while high doses have anti-progesterone activity, which inhibits the development of endometrial glands and affects the rate that the zygote moves, which does not synchronize with the development of the endometrium and detrimental to implantation. Most of the existing synthesis methods are using sulfuric acid solution and chromium oxide as reactants. As sulfuric acid as reactant will increase the risk coefficient of reaction process, it is not conducive to safe production. Chromium oxide as a reactant will increase the degree of pollution to the environment, and it does not meet the requirements of green environmental protection, and the synthesis method is complicated. Therefore, it is necessary to propose a new synthesis method.
SUMMARY
Based on the technical problems of the background technology, the purpose of the present invention is to provide pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method, comprises
2018100820 19 Jun 2018 the following steps:
A: androstane-l,4-dichloro-2p,3P-glycol-17 ketone,900ml diethylbenzene solution were added to the reaction vessel, raised the temperature of the solution to
40-47°C, controlled the stirring speed at 130-150rpm, added 1.7ml potassium nitrate 5 solution, reacted for 90-110 min;
B: continued to add antimony trioxide anhydride, glycerol ester solution, raised the temperature of the solution to 60-65 °C, reacted for 40-60min, filter, diluted with potassium chloride solution, added oxalic acid solution to adjust pH to 4-5, lay up for 2-3h,reduced the temperature of the solution to 10-15°C, washed with the sodium sulfate solution, washed with the 2-cycloheptanone solution, re-crystallized in the dimethyl disulfide solution, dehydrated with dehydration, got the finished product androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid.
Preferably, the diethylbenzene solution has a mass fraction of 10-17%.
Preferably, the mass fraction of the potassium nitrate solution is 20-26%.
Preferably, the glycerol ester solution has a mass fraction of 35-43%.
Preferably, the potassium chloride solution has a mass fraction of 15-21%.
Preferably, the mass fraction of oxalic acid solution is 10-16%.
Preferably, the sodium sulfate solution has a mass fraction of 20-25%.
Preferably, the 2-cycloheptanone solution has a mass fraction of 50-57%.
Preferably, the mass fraction of dimethyl disulfide solution is 80-86%.
Throughout the reaction process can be the following reaction formula:
Compared with the synthetic method disclosed in the background art, the invention provides pharmaceutical intermediates androstane-2,3-break-17-ketone-2,
3-dicarboxylic acid synthesis method, it is unnecessary to use sulfuric acid solution and
2018100820 19 Jun2018 chromium oxide as reactants, and it will decrease the risk coefficient of reaction process by sulfuric acid, it is conducive to safe production and avoid the environmental pollution of chromium oxide as a reactant, and meet the requirements of green environmental protection, reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, the present invention provides a new synthetic route which has laid a good foundation for further enhancing the yield of the reaction.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method, comprises the following steps:
A: 3 mol androstane-l,4-dichloro-2p,3p-glycol -17 ketone,900ml diethylbenzene solution with a mass fraction of 10% were added to the reaction vessel, raised the temperature of the solution to 40°C, controlled the stirring speed at 130rpm, added 1.7ml potassium nitrate solution with a mass fraction of 20%, reacted for 90 min;
B: continued to add 3 mol antimony trioxide anhydride, 6 mol glycerol ester solution with a mass fraction of 35%, raised the temperature of the solution to 60 °C, reacted for 40min, filter, diluted with potassium chloride solution with a mass fraction of 15%, added oxalic acid solution with a mass fraction of 10% to adjust pH to 4, lay up for 2h,reduced the temperature of the solution to 10 °C, washed with the sodium sulfate solution with a mass fraction of 20%, washed with the 2-cycloheptanone solution with a mass fraction of 50%, re-crystallized in the dimethyl disulfide solution with a mass fraction of 80%, dehydrated with anhydrous calcium chloride dehydration, got the finished product androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid 910.8g, yield of 92%.
2018100820 19 Jun 2018
Embodiment 2
Pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method, comprises the following steps:
A: 3 mol androstane-l,4-dichloro-2p,3p-glycol -17 ketone,900ml diethylbenzene 5 solution with a mass fraction of 15% were added to the reaction vessel, raised the temperature of the solution to 44°C, controlled the stirring speed at 140rpm, added
1.7ml potassium nitrate solution with a mass fraction of 23%, reacted for 100 min;
B: continued to add 3.5 mol antimony trioxide anhydride, 6.5 mol glycerol ester solution with a mass fraction of 38%, raised the temperature of the solution to 63 °C, reacted for 50min, filter, diluted with potassium chloride solution with a mass fraction of 18%, added oxalic acid solution with a mass fraction of 14% to adjust pH to 4.5, lay up for 2.5h,reduced the temperature of the solution to 13°C, washed with the sodium sulfate solution with a mass fraction of 23%, washed with the
2- cycloheptanone solution with a mass fraction of 53%, re-crystallized in the dimethyl disulfide solution with a mass fraction of 83%, dehydrated with activated alumina dehydration, got the finished product androstane-2,3-break-17-ketone-2,
3- dicarboxylic acid 930.6g, yield of 94%.
Embodiment 3
Pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method, comprises the following steps:
A: 3 mol androstane-l,4-dichloro-2p,3p-glycol -17 ketone,900ml diethylbenzene solution with a mass fraction of 17% were added to the reaction vessel, raised the temperature of the solution to 47°C, controlled the stirring speed at 150rpm, added
1.7ml potassium nitrate solution with a mass fraction of 26%, reacted for 110 min;
B: continued to add 4 mol antimony trioxide anhydride, 7 mol glycerol ester solution with a mass fraction of 43%, raised the temperature of the solution to 65 °C, reacted for 60min, filter, diluted with potassium chloride solution with a mass fraction
2018100820 19 Jun 2018 of 21%, added oxalic acid solution with a mass fraction of 16% to adjust pH to 5, lay up for 3h,reduced the temperature of the solution to 15 °C, washed with the sodium sulfate solution with a mass fraction of 25%, washed with the 2-cycloheptanone solution with a mass fraction of 57%, re-crystallized in the dimethyl disulfide solution with a mass fraction of 86%, dehydrated with anhydrous sodium sulfate dehydration, got the finished product androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid 960.3g, yield of 97%.
The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.
2018100820 19 Jun 2018
Claims (4)
- Claims1. Pharmaceutical intermediates androstane-2,3-break-17-ketone-2,3-dicarboxylic acid synthesis method, comprises the following steps:A: androstane-l,4-dichloro-2p,3p-glycol-17 ketone,900ml diethylbenzene solution were added to the reaction vessel, raised the temperature of the solution to 40-47°C, controlled the stirring speed at 130-150rpm, added 1.7ml potassium nitrate solution, reacted for 90-110 min;B: continued to add antimony trioxide anhydride, glycerol ester solution, raised 10 c the temperature of the solution to 60-65°C, reacted for 40-60min, filter, diluted with potassium chloride solution, added oxalic acid solution to adjust pH to 4-5, lay up for
- 2- 3h,reduced the temperature of the solution to 10-15 °C, washed with the sodium sulfate solution, washed with the 2-cycloheptanone solution, re-crystallized in the dimethyl disulfide solution, dehydrated with dehydration, got the finished product 15 androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid.2. Pharmaceutical intermediates androstane-2,3-break-17-ketone-2,
- 3- dicarboxylic acid synthesis method according to claim 1 wherein the diethylbenzene solution has a mass fraction of 10-17%.3. Pharmaceutical intermediates androstane-2,3-break-17-ketone-2,20 3-dicarboxylic acid synthesis method according to claim 1 wherein the mass fraction of the potassium nitrate solution is 20-26%.
- 4. Pharmaceutical intermediates androstane-2,3-break-17-ketone-2,3-dicarboxylic acid synthesis method according to claim 1 wherein the glycerol ester solution has a mass fraction of 35-43%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2017105266170 | 2017-07-01 | ||
| CN201710526617.0A CN108238908A (en) | 2017-07-01 | 2017-07-01 | Pharmaceutical intermediate androstane -2,3- breaks the synthetic methods of the double carboxylic acids of -17- ketone -2,3- |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100820A4 true AU2018100820A4 (en) | 2018-08-09 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018100820A Ceased AU2018100820A4 (en) | 2017-07-01 | 2018-06-19 | Pharmaceutical intermediates androstane-2,3-break-17-ketone-2, 3-dicarboxylic acid synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108238908A (en) |
| AU (1) | AU2018100820A4 (en) |
| GB (1) | GB201713392D0 (en) |
| IE (1) | IE20180194U1 (en) |
-
2017
- 2017-07-01 CN CN201710526617.0A patent/CN108238908A/en active Pending
- 2017-08-21 GB GBGB1713392.7A patent/GB201713392D0/en not_active Ceased
-
2018
- 2018-06-19 AU AU2018100820A patent/AU2018100820A4/en not_active Ceased
- 2018-06-26 IE IES20180194A patent/IE20180194U1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE20180194U1 (en) | 2020-06-24 |
| CN108238908A (en) | 2018-07-03 |
| GB201713392D0 (en) | 2017-10-04 |
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