AU2018100817A4 - 4-pregnene-16α-methyl-17α-mellow-3, 20-diketone drug synthesis method - Google Patents
4-pregnene-16α-methyl-17α-mellow-3, 20-diketone drug synthesis method Download PDFInfo
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- AU2018100817A4 AU2018100817A4 AU2018100817A AU2018100817A AU2018100817A4 AU 2018100817 A4 AU2018100817 A4 AU 2018100817A4 AU 2018100817 A AU2018100817 A AU 2018100817A AU 2018100817 A AU2018100817 A AU 2018100817A AU 2018100817 A4 AU2018100817 A4 AU 2018100817A4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/004—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa
- C07J7/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa substituted in position 16
- C07J7/0055—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
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- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Abstract
4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug synthesis method Abstract 5 The present invention discloses 4-pregnene- I 6a-methyl- 1 7u-mellow-3, 20-diketone drug synthesis method, comprises the following steps:, comprises the following steps: 2-bromo-4-amino-5-pregnene-16ax-methyl-3 p, 17a-glycol-20-ketone, and potassium nitrate solution were added to the reaction vessel, controlled the stirring speed, raised the temperature of the solution, continued to react; added butyric 10 acid methyl ester solution to react, raised the temperature of the solution, continued to react, then added tetrakis (triethyl phosphite) nickel powder, refluxed, reduced the temperature of the solution, added the oxalic acid solution, lay up to get hierarchical solution, washed with the potassium chloride solution for several times, washed with 2-butylene-1,4-diacid solution for several times, washed with the p-xylene solution 15 for several times, re-crystallized in the dimethyl sulfone solution, dehydrated with dehydration, got the finished product 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug.
Description
The present invention discloses 4-pregnene-16a-methyl-17a-mellow-3,
20-diketone drug synthesis method, comprises the following steps:, comprises the following steps: 2-bromo-4-amino-5-pregnene-16a-methyl-3p, 17a-glycol-20-ketone, and potassium nitrate solution were added to the reaction vessel, controlled the stirring speed, raised the temperature of the solution, continued to react; added butyric acid methyl ester solution to react, raised the temperature of the solution, continued to react, then added tetrakis (triethyl phosphite) nickel powder, refluxed, reduced the temperature of the solution, added the oxalic acid solution, lay up to get hierarchical solution, washed with the potassium chloride solution for several times, washed with 2-butylene-l,4-diacid solution for several times, washed with the p-xylene solution for several times, re-crystallized in the dimethyl sulfone solution, dehydrated with dehydration, got the finished product 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug.
2018100817 19 Jun 2018
4-pregnene-l6<x-methyl- 17a-mellow-3, 20-diketone drug synthesis method
FIELD OF THE INVENTION
The present invention relates to a method for preparing a pharmaceutical 5 intermediate which belongs to the field of organic synthesis, more particularly, relates to 4-pregnene-16a-methyl-17(x-mellow-3, 20-diketone drug synthesis method.
GENERAL BACKGROUND
4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug is a kind of hormone pharmaceutical intermediates. It is used for the production of dexamethasone acetate which belongs to adrenal cortical hormone and adrenocorticotropic hormone, it can be used for anti-skin mucosal inflammation and allergic reactions, eye ointment can be used for the treatment various ophthalmia. However, most of the existing synthesis methods are using the mixed solution of chromium oxide and sulfuric acid as one of reactions, chromic oxide results in environmental pollution, sulfuric acid attributes to high-risk chemicals factor, 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 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug synthesis method, comprises the following steps:
A: 2-bromo-4-amino-5-pregnene-16a-methyl-3p, 17a-glycol-20-ketone, and 1.5 L potassium nitrate solution were added to the reaction vessel, controlled the stirring speed at 110-150 rpm, raised the temperature of the solution to 40-47 °C , continued to react for 60-80 min;
B: added butyric acid methyl ester solution to react, raised the temperature of the solution to 50-56 °C , continued to react for 30-40min, then added tetrakis (triethyl
2018100817 19 Jun 2018 phosphite) nickel powder, refluxed for 30-50min, reduced the temperature of the solution to 30-36°C, added the oxalic acid solution, lay up for 1-2 hours to get hierarchical solution, washed with the potassium chloride solution for several times, washed with 2- butylene-1,4-diacid solution for several times, washed with the p-xylene solution for several times, re-crystallized in the dimethyl sulfone solution, dehydrated with dehydration, got the finished product 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug.
Preferably, the potassium nitrate solution has a mass fraction of 10-16%. Preferably, the mass fraction of the butyric acid methyl ester solution is 35-39%.
Preferably, the potassium chloride solution has a mass fraction of 15-19%.
Preferably, the 2-butylene-1,4-diacid solution has a mass fraction of 50-56%. Preferably, the mass fraction of p-xylene solution is 60-65%.
Preferably, the mass fraction of dimethyl sulfone solution is 80-87%.
Throughout the reaction process can be the following reaction formula:
Compared with the synthetic method disclosed in the background art, the invention provides 4-pregnene-16a- methyl-17a-mellow-3, 20-diketone drug synthesis method, it is unnecessary to use the mixed solution of chromium oxide and sulfuric acid as reaction, avoiding the environmental pollution caused by chromic oxide and the influence of high-risk chemicals on the safety factor caused by sulfuric acid, 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.
2018100817 19 Jun 2018
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug synthesis method, comprises the following steps:
A: 3mol 2-bromo-4-amino-5-pregnene-16a-methyl-3p, 17a-glycol-20-ketone, and 1.5 L potassium nitrate solution with a mass fraction of 10% were added to the reaction vessel, controlled the stirring speed at 110 rpm, raised the temperature of the solution to 40 °C , continued to react for 60min;
B: added 6mol methyl butyric acid methyl ester solution with a mass fraction of 35% to react, raised the temperature of the solution to 50 °C , continued to react for 30min, then added 2mol tetrakis (triethyl phosphite) nickel powder, refluxed for 30min, reduced the temperature of the solution to 30 °C, added the oxalic acid solution, lay up for lhours to get hierarchical solution, washed with the potassium chloride solution with a mass fraction of 15% for three times, washed with 2-butylene-l,4-diacid solution with a mass fraction of 50% for five times, washed with the p-xylene solution with a mass fraction of 60% for six times, re-crystallized in the dimethyl sulfone solution with a mass fraction of 80%, dehydrated with anhydrous sodium sulfate dehydration, got the finished product 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug 895.23g, yield of 87%.
Embodiment 2
4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug synthesis method, comprises the following steps:
A: 3mol 2-bromo-4-amino-5-pregnene-16a-methyl-3p, 17a-glycol-20-ketone, and 1.5 L potassium nitrate solution with a mass fraction of 15% were added to the reaction vessel, controlled the stirring speed at 130 rpm, raised the temperature of the solution to 45 °C , continued to react for 70min;
2018100817 19 Jun 2018
B: added 6.5mol methyl butyric acid methyl ester solution with a mass fraction of 37% to react, raised the temperature of the solution to 53 °C , continued to react for 35min, then added 2.5mol tetrakis (triethyl phosphite) nickel powder, refluxed for 40min, reduced the temperature of the solution to 34 °C, added the oxalic acid solution, lay up for 1.5 hours to get hierarchical solution, washed with the potassium chloride solution with a mass fraction of 17% for four times, washed with 2-butylene-l,4-diacid solution with a mass fraction of 54% for six times, washed with the p-xylene solution with a mass fraction of 63% for eight times, re-crystallized in the dimethyl sulfone solution with a mass fraction of 82%, dehydrated with anhydrous calcium sulphate dehydration, got the finished product 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug 936.39g, yield of 91%.
Embodiment 3
4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug synthesis method, comprises the following steps:
A: 3mol 2-bromo-4-amino-5-pregnene-16a-methyl-3(:5, 17a-glycol-20-ketone, and 1.5 L potassium nitrate solution with a mass fraction of 16% were added to the reaction vessel, controlled the stirring speed at 150 rpm, raised the temperature of the solution to 47°C , continued to react for 80min;
B: added 7mol methyl butyric acid methyl ester solution with a mass fraction of 39% to react, raised the temperature of the solution to 56°C , continued to react for 40min, then added 3mol tetrakis (triethyl phosphite) nickel powder, refluxed for 50min, reduced the temperature of the solution to 36 °C, added the oxalic acid solution, lay up for 2 hours to get hierarchical solution, washed with the potassium chloride solution with a mass fraction of 19% for five times, washed with 2-butylene-l,4-diacid solution with a mass fraction of 56% for seven times, washed with the p-xylene solution with a mass fraction of 65% for nine times, re-crystallized in the dimethyl sulfone solution with a mass fraction of 87%, dehydrated with anhydrous potassium carbonate dehydration, got the finished product 4-pregnene-16a-methyl-17a-mellow-3,
2018100817 19 Jun 2018
20-diketone drug 956.97g, yield of 93%.
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.
2018100817 19 Jun 2018
Claims (4)
- Claims1. 4-pregnene-16a-methyl-17α-mellow-3, 20-diketone drug synthesis method, comprises the following steps:5 A: 2-bromo-4-amino-5-pregnene-16a-methyl-3p, 17a-glycol-20-ketone, and 1.5L potassium nitrate solution were added to the reaction vessel, controlled the stirring speed at 110-150 rpm, raised the temperature of the solution to 40-47 °C, continued to react for 60-80 min;B: added butyric acid methyl ester solution to react, raised the temperature of the10 solution to 50-56 °C, continued to react for 30-40min, then added tetrakis (triethyl phosphite) nickel powder, refluxed for 30-50min, reduced the temperature of the solution to 30-36Ό, added the oxalic acid solution, lay up for 1-2 hours to get hierarchical solution, washed with the potassium chloride solution for several times, washed with 2- butylene -1,4-diacid solution for several times, washed with the15 p-p-xylene solution for several times, re-crystallized in the dimethyl sulfone solution, dehydrated with dehydration, got the finished product 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug.
- 2. 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug synthesis method according to claim 1 wherein potassium nitrate solution has a mass fraction of20 10-16%.
- 3. 4-pregnene-16a-methyl-17a-mellow-3, 20-diketone drug synthesis method according to claim 1 wherein the mass fraction of the butyric acid methyl ester solution is 35-39%.
- 4. 4-pregnene-l6a-methyl-17a-mellow-3, 20-diketone drug synthesis method25 according to claim 1 wherein the potassium chloride solution has a mass fraction of15-19%
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710526846.2A CN108239133A (en) | 2017-06-30 | 2017-06-30 | The synthetic method of -17 α -ol -3,20- diketone drugs of -16 Alpha-Methyl of 4- pregnenes |
| CN2017105268462 | 2017-06-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100817A4 true AU2018100817A4 (en) | 2018-08-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018100817A Ceased AU2018100817A4 (en) | 2017-06-30 | 2018-06-19 | 4-pregnene-16α-methyl-17α-mellow-3, 20-diketone drug synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108239133A (en) |
| AU (1) | AU2018100817A4 (en) |
| GB (1) | GB201713386D0 (en) |
| IE (1) | IES20180212A2 (en) |
-
2017
- 2017-06-30 CN CN201710526846.2A patent/CN108239133A/en active Pending
- 2017-08-21 GB GBGB1713386.9A patent/GB201713386D0/en not_active Ceased
-
2018
- 2018-06-19 AU AU2018100817A patent/AU2018100817A4/en not_active Ceased
- 2018-06-26 IE IES20180212 patent/IES20180212A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN108239133A (en) | 2018-07-03 |
| IES20180212A2 (en) | 2019-11-13 |
| GB201713386D0 (en) | 2017-10-04 |
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