AU2018100819A4 - Pharmaceutical hormone intermediates 11-ketone-16alpha, 17alpha-epoxy progesterone synthesis method - Google Patents
Pharmaceutical hormone intermediates 11-ketone-16alpha, 17alpha-epoxy progesterone synthesis method Download PDFInfo
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- AU2018100819A4 AU2018100819A4 AU2018100819A AU2018100819A AU2018100819A4 AU 2018100819 A4 AU2018100819 A4 AU 2018100819A4 AU 2018100819 A AU2018100819 A AU 2018100819A AU 2018100819 A AU2018100819 A AU 2018100819A AU 2018100819 A4 AU2018100819 A4 AU 2018100819A4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
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Abstract
Pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method Abstract The present invention discloses pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method, comprises the following steps: 2-bromine-ila-hydroxy-14-amino-16a, 17a-epoxy progesterone, sodium sulfate solution were added to the reaction vessel, controlled the stirring speed, 10 controlled the temperature of the solution, reacted; added furan carboxylic acid ethyl ester solution and antimony trichloride powder, raised the temperature of the solution, reacted, added potassium chloride solution, lay up, got crystal, filter, washed with the sodium nitrate solution for several times, washed with the 2,6-dimethyl pyridine solution for several times, washed with the difluorodichloromethane solution for 15 several times, re-crystallized in the diethylene glycol ether solution, dehydrated with dehydration, got the finished product 11 -ketone- 1 6a, 17a-epoxy progesterone.
Description
The present invention discloses pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method, comprises the following steps: 2-bromine-lla-hydroxy-14-amino-16a, 17a-epoxy progesterone, sodium sulfate solution were added to the reaction vessel, controlled the stirring speed, controlled the temperature of the solution, reacted; added furan carboxylic acid ethyl ester solution and antimony trichloride powder, raised the temperature of the solution, reacted, added potassium chloride solution, lay up, got crystal, filter, washed with the sodium nitrate solution for several times, washed with the 2,6-dimethyl pyridine solution for several times, washed with the difluorodichloromethane solution for several times, re-crystallized in the diethylene glycol ether solution, dehydrated with dehydration, got the finished product 11-ketone-16a, 17a-epoxy progesterone.
2018100819 19 Jun 2018
Pharmaceutical hormone intermediates ll-ketone-16a, 17a-epoxy progesterone 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 hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method.
GENERAL BACKGROUND
11-ketone-16a, 17a-epoxy progesterone is a kind of pharmaceutical hormone intermediates. It is used for the production of cortisone, cortisone acetate which has the anti-inflammatory agent function is the intermediate of prednisone acetate, and it is mainly used to treat the adrenal cortical dysfunction, rheumatoid arthritis, rheumatism, lupus erythematosus and other diseases. However, most of the existing synthesis methods are using the chromium oxide, manganese chloride and acetic acid as reactants. Because of chromium oxide and manganese pollutes environment heavily, the reaction process does not meet the requirements of environmental protection, the pollution treatment is of higher physical cost, 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 hormone intermediates 11-ketone-16a,
17a-epoxy progesterone synthesis method, comprises the following steps:
A: 2-bromine-lla-hydroxy-14-amino-16a, 17a-epoxy progesterone, 1.8 L sodium sulfate solution were added to the reaction vessel, controlled the stirring speed at 150-170rpm, controlled the temperature of the solution to 10-16°C, reacted for 50-70 min;
B: added furan carboxylic acid ethyl ester solution and antimony trichloride
2018100819 19 Jun 2018 powder, raised the temperature of the solution to 30-35 °C, reacted for l-2h, added 2 L potassium chloride solution, lay up for 2-3h, got crystal, filter, washed with the sodium nitrate solution for several times, washed with the 2,6-dimethyl pyridine solution for several times, washed with the difluorodichloromethane solution for several times, re-crystallized in the diethylene glycol ether solution, dehydrated with dehydration, got the finished product 11-ketone-16a, 17a-epoxy progesterone.
Preferably, the sodium sulfate solution has a mass fraction of 15-22%.
Preferably, the mass fraction of the furan carboxylic acid ethyl ester solution is
20-25%.
Preferably, the potassium chloride solution has a mass fraction of 10-17%.
Preferably, the sodium nitrate solution has a mass fraction of 20-26%.
Preferably, the mass fraction of 2, 6-dimethyl pyridine solution is 50-57%. Preferably, the difluorodichloromethane solution has a mass fraction of 55-62%. Preferably, the mass fraction of diethylene glycol ether 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 hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method, it is unnecessary to use chromium oxide, manganese chloride and acetic acid as reactants, avoiding the environmental pollution of chromium oxide and manganese chloride and the reaction process meets the requirements of environmental protection, reducing pollution treatment cost, 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
2018100819 19 Jun 2018 invention are further illustrated:
Embodiment 1
Pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method, comprises the following steps:
A: 2 mol 2-bromine-lla-hydroxy-14-amino-16a, 17a-epoxy progesterone, 1.8 L sodium sulfate solution with a mass fraction of 15%were added to the reaction vessel, controlled the stirring speed at 150rpm, controlled the temperature of the solution to KFC, react for 50min;
B: added 4 mol furan carboxylic acid ethyl ester solution with a mass fraction of 10 20% and 2 mol antimony trichloride powder, raised the temperature of the solution to
30°C, reacted for lh, added 2 L potassium chloride solution with a mass fraction of 10%, lay up for 2h,got crystal, filter, washed with the sodium nitrate solution with a mass fraction of 20% for two times, washed with the 2,6-dimethyl pyridine solution with a mass fraction of 50% for four times, washed with the difluorodichloromethane solution with a mass fraction of 55% for three times, re-crystallized in the diethylene glycol ether solution with a mass fraction of 80%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished product 11-ketone-16a, 17a-epoxy progesterone 673.74g, yield of 98.5%.
Embodiment 2
Pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method, comprises the following steps:
A: 2 mol 2-bromine-lla-hydroxy-14-amino-16a, 17a-epoxy progesterone, 1.8 L sodium sulfate solution with a mass fraction of 17%were added to the reaction vessel, controlled the stirring speed at 160rpm, controlled the temperature of the solution to
14°C, react for 60min;
B: added 5 mol furan carboxylic acid ethyl ester solution with a mass fraction of 23% and 2.5 mol antimony trichloride powder, raised the temperature of the solution to 34°C, reacted for 1.5h, added 2 L potassium chloride solution with a mass fraction of 15%, lay up for 2.5h,got crystal, filter , washed with the sodium nitrate solution with a mass fraction of 24% for three times, washed with the 2,6-dimethyl pyridine solution
2018100819 19 Jun2018 with a mass fraction of 55% for five times, washed with the difluorodichloromethane solution with a mass fraction of 59% for four times, re-crystallized in the diethylene glycol ether solution with a mass fraction of 85%, dehydrated with activated alumina dehydration, got the finished product 11-ketone-16a, 17a-epoxy progesterone
1017.792g, yield of 99.2%.
Embodiment 3
Pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method, comprises the following steps:
A: 2 mol 2-bromine-lla-hydroxy-14-amino-16a, 17a-epoxy progesterone, 1.8 L sodium sulfate solution with a mass fraction of 22%were added to the reaction vessel, controlled the stirring speed at 170rpm, controlled the temperature of the solution to 16°C, react for 70min;
B: added 6 mol furan carboxylic acid ethyl ester solution with a mass fraction of 25% and 3 mol antimony trichloride powder, raised the temperature of the solution to
35 °C, reacted for 2h, added 2 L potassium chloride solution with a mass fraction of 17%, lay up for 3h,got crystal, filter, washed with the sodium nitrate solution with a mass fraction of 26% for four times, washed with the 2,6-dimethyl pyridine solution with a mass fraction of 57% for six times, washed with the difluorodichloromethane solution with a mass fraction of 62% for five times, re-crystallized in the diethylene glycol ether solution with a mass fraction of 86%, dehydrated with anhydrous calcium chloride dehydration, got the finished product 11-ketone-16a, 17a-epoxy progesterone 1021.896g, yield of 99.6%.
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.
2018100819 19 Jun 2018
Claims (4)
- Claims1. Pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method, comprises the following steps:5 A: 2-bromine-ll a -hydroxy- 14-amino- 16a, 17a-epoxy progesterone, 1.8 L sodium sulfate solution were added to the reaction vessel, controlled the stirring speed at 150-170rpm, controlled the temperature of the solution to 10-16°C, reacted for 50-70 min;B: added furan carboxylic acid ethyl ester solution and antimony trichloride 10 < , powder, raised the temperature of the solution to 30-35 °C, reacted for l-2h, added 2 L potassium chloride solution, lay up for 2-3h, got crystal, filter, washed with the sodium nitrate solution for several times, washed with the 2,6-dimethyl pyridine solution for several times, washed with the difluorodichloromethane solution for several times, re-crystallized in the diethylene glycol ether solution, dehydrated with dehydration, got the finished product 11-ketone-16a, 17a-epoxy progesterone.
- 2. Pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method according to claim 1 wherein the sodium sulfate solution has a mass fraction of 15-22%.
- 3. Pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy20 progesterone synthesis method according to claim 1 wherein the mass fraction of the furan carboxylic acid ethyl ester solution is 20-25%.
- 4. Pharmaceutical hormone intermediates 11-ketone-16a, 17a-epoxy progesterone synthesis method according to claim 1 wherein the potassium chloride solution has a mass fraction of 10-17%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710527156.9A CN108239137A (en) | 2017-07-01 | 2017-07-01 | Medical -16 α of hormone intermediate 11- ketone, the synthetic method of 17 α-epoxy progesterone |
| CN2017105271569 | 2017-07-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100819A4 true AU2018100819A4 (en) | 2018-08-02 |
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| Application Number | Title | Priority Date | Filing Date |
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| AU2018100819A Ceased AU2018100819A4 (en) | 2017-07-01 | 2018-06-19 | Pharmaceutical hormone intermediates 11-ketone-16alpha, 17alpha-epoxy progesterone synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108239137A (en) |
| AU (1) | AU2018100819A4 (en) |
| GB (1) | GB201713391D0 (en) |
| IE (1) | IES20180195A2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019037743A1 (en) * | 2017-08-22 | 2019-02-28 | 中国石油化工股份有限公司 | Starch-containing microsphere and preparation method therefor and application thereof |
-
2017
- 2017-07-01 CN CN201710527156.9A patent/CN108239137A/en active Pending
- 2017-08-21 GB GBGB1713391.9A patent/GB201713391D0/en not_active Ceased
-
2018
- 2018-06-19 AU AU2018100819A patent/AU2018100819A4/en not_active Ceased
- 2018-06-26 IE IES20180195 patent/IES20180195A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| GB201713391D0 (en) | 2017-10-04 |
| CN108239137A (en) | 2018-07-03 |
| IES20180195A2 (en) | 2019-11-13 |
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