IES87003B2 - Drug intermediates 3-ene hexenoic acid synthesis method - Google Patents
Drug intermediates 3-ene hexenoic acid synthesis method Download PDFInfo
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- IES87003B2 IES87003B2 IES20180191A IES20180191A IES87003B2 IE S87003 B2 IES87003 B2 IE S87003B2 IE S20180191 A IES20180191 A IE S20180191A IE S20180191 A IES20180191 A IE S20180191A IE S87003 B2 IES87003 B2 IE S87003B2
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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
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The present invention discloses drug intermediates 3-ene hexenoic acid synthesis method, comprises the following steps: 2-bromine-3-hexene-l-ketone, potassium nitrate solution were added to the reaction vessel, controlled the stirring speed, controlled the temperature of the solution, reacted, added isopropyl butyrate solution, raised the temperature of the solution, continued to react; added molybdenum dichloride powder, controlled the stirring speed, reacted, washed with the diethylene glycol ethereal solution for several times, washed with the potassium bromide solution for several times, added tri-chlorine acetic acid solution, adjusted the PH, washed with the sulfolane solution for several times, then merged, continued to wash with bromoethane solution, washed with ethoxybenzene solution, re-crystallized in the N, N-dibutylaniline solution, dehydrated with dehydration, got the finished product 3-ene hexenoic acid. <Figure 1>
Description
The present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to drug intermediates 3-ene hexenoic acid synthesis method.
GENERAL BACKGROUND
3-ene hexenoic acid is mainly used as intermediates in the synthesis of drugs, most of the existing synthesis methods are using the process that chromium trioxide, sulfuric acid and water used as reactants, the reaction is usually carried out at low temperatures, because the chromium trioxide is more polluting to the environment, the cost of follow-up pollution treatment is higher, the sulfuric acid which acts as a reactant will increase the risk coefficient of the reaction process, moreover, the reaction process needs to maintain the low temperature environment, and the energy consumption of the reaction process is higher, the reaction cost will increase rapidly in the actual production process, 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 drug intermediates 3-ene hexenoic acid synthesis method, comprises the following steps:
A: 2-bromine-3-hexene-1-ketone, 1.6L potassium nitrate solution were added to the reaction vessel, controlled the stirring speed at 110-130rpm, controlled the temperature of the solution to 30-36°C, reacted for 50-70min, added isopropyl butyrate solution, raised the temperature of the solution to 40-45 °C, continued to react for l-2h;
B: added molybdenum dichloride powder, controlled the stirring speed at
220-250rpm, reacted for 60-90min, washed with the diethyllene glycol ethereal solution for several times, washed with the potassium bromide solution for several times, added tri-chlorine acetic acid solution, adjusted the PH to 4-5, washed with the sulfolane solution for several times, then merged, continued to wash with bromoethane solution, washed with ethoxybenzene solution, re-crystallized in the N, N-dibutylaniline solution, dehydrated with dehydration, got the finished product 3-ene hexenoic acid.
Preferably, the potassium nitrate solution has a mass fraction of 10-16%.
Preferably, the mass fraction of the isopropyl butyrate solution is 30-37%.
Preferably, the mass fraction of the diethyllene glycol ethereal solution is 45-52%.
Preferably, the potassium bromide solution has a mass fraction of 15-21%.
Preferably, the mass fraction of tri-chlorine acetic acid solution is 20-24%.
Preferably, the sulfolane solution has a mass fraction of 50-55%.
Preferably, the mass fraction of bromoethane solution is 60-66%.
Preferably, the mass fraction of ethoxybenzene solution is 70-77%.
Preferably, the mass fraction of the N, N-dibutylaniline solution is 80-85%.
Throughout the reaction process can be the following reaction formula:
CH3 |CH3
H2cI
CH OH || II GH hc\ /ch IIII
CH + C7Hi4O2 + Mo(x .HC
COH
IH
Br
Compared with the synthetic method disclosed in the background art, the invention provides drug intermediates 3-ene hexenoic acid synthesis method, it is unnecessary to use chromium trioxide, sulfuric acid and water as reactions and the reaction is not need to be carried out at low temperatures, avoiding the environmental pollution of chromium trioxide and reducing the cost of follow-up pollution treatment, meanwhile avoiding the high-risk of decreasing 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 offered a good foundation for further enhancing the yield of reaction.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Drug intermediates 3-ene hexenoic acid synthesis method comprises the following steps:
A: 2mol 2-bromine-3-hexene-l-ketone, 1.6L potassium nitrate solution with a mass fraction of 10% were added to the reaction vessel, controlled the stirring speed at 11 Orpm, controlled the temperature of the solution to 30°C, reacted for 50min, added 4mol isopropyl butyrate solution with a mass fraction of 30%, raised the temperature of the solution to 40 °C, continued to react for lh;
B: added 3mol molybdenum dichloride powder, controlled the stirring speed at 220rpm, reacted for 60min, washed with the diethyllene glycol ethereal solution with a mass fraction of 45% for two times, washed with the potassium bromide solution with a mass fraction of 15% for four times, added tri-chlorine acetic acid solution with a mass fraction of 20%, adjusted the PH to 4, washed with the sulfolane solution with a mass fraction of 50% for three times, then merged, continued to wash with bromoethane solution with a mass fraction of 60%, washed with ethoxybenzene solution with a mass fraction of 70%, re-crystallized in the N, N-dibutylaniline solution with a mass fraction of 80%, dehydrated with anhydrous potassium carbonate dehydration, got the finished product 3-ene hexenoic acid 198.36g, yield of 87%.
Embodiment 2
Drug intermediates 3-ene hexenoic acid synthesis method comprises the following steps:
A: 2mol 2-bromine-3-hexene-1 -ketone, 1.6L potassium nitrate solution with a mass fraction of 13% were added to the reaction vessel, controlled the stirring speed at 120rpm, controlled the temperature of the solution to 33°C, reacted for 60min, added 4.5mol isopropyl butyrate solution with a mass fraction of 33.5%, raised the temperature of the solution to 42.5 °C, continued to react for 1.5h;
B: added 3.5mol molybdenum dichloride powder, controlled the stirring speed at 230rpm, reacted for 75min, washed with the diethyllene glycol ethereal solution with a 5 mass fraction of 47% for three times, washed with the potassium bromide solution with a mass fraction of 17% for five times, added tri-chlorine acetic acid solution with a mass fraction of 22%, adjusted the PH to 4.5, washed with the sulfolane solution with a mass fraction of 52.5% for four times, then merged, continued to wash with bromoethane solution with a mass fraction of 63%, washed with ethoxybenzene 10 solution with a mass fraction of 73.5%, re-crystallized in the N, N-dibutylaniline solution with a mass fraction of 82.5%, dehydrated with anhydrous calcium sulphate dehydration, got the finished product 3-ene hexenoic acid 207.48g, yield of 91%.
Embodiment 3
Drug intermediates 3-ene hexenoic acid synthesis method comprises the following steps:
A: 2mol 2-bromine-3-hexene-1-ketone, 1.6L potassium nitrate solution with a mass fraction of 16% were added to the reaction vessel, controlled the stirring speed at 130rpm, controlled the temperature of the solution to 36°C, reacted for 70min, 20 added 5mol isopropyl butyrate solution with a mass fraction of 37%, raised the temperature of the solution to 45 °C, continued to react for 2h;
B: added 4mol molybdenum dichloride powder, controlled the stirring speed at 250rpm, reacted for 90min, washed with the diethyllene glycol ethereal solution with a mass fraction of 52%> for four times, washed with the potassium bromide solution with 25 a mass fraction of 21% for six times, added tri-chlorine acetic acid solution with a mass fraction of 24%, adjusted the PH to 5, washed with the sulfolane solution with a mass fraction of 55% for five times, then merged, continued to wash with bromoethane solution with a mass fraction of 66%, washed with ethoxybenzene solution with a mass fraction of 77%, re-crystallized in the N, N-dibutylaniline solution with a mass fraction 30 of 85%, dehydrated with phosphorus pentoxide dehydration, got the finished product
3-ene hexenoic acid 214.32g, yield of 94%.
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 5 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.
Claims (4)
1. Drug intermediates 3-ene hexenoic acid synthesis method, comprise the following steps: A: 2-bromine-3-hexene-1-ketone, 1.6L potassium nitrate solution were added to the reaction vessel, controlled the stirring speed at 110-130rpm, controlled the temperature of the solution to 30-36°C, reacted for 50-70min, added isopropyl butyrate solution, raised the temperature of the solution to 40-45 °C, continued to react for 1 -2h; B. added molybdenum dichloride powder, controlled the stirring speed at 220-250rpm, reacted for 60-90min, washed with the diethyllene glycol ethereal solution for several times, washed with the potassium bromide solution for several times, added tri-chlorine acetic acid solution, adjusted the PH to 4-5, washed with the sulfolane solution for several times, then merged, continued to wash with bromoethane solution, washed with ethoxybenzene solution, re-crystallized in the N, N-dibutylaniline solution, dehydrated with dehydration, got the finished product 3-ene hexenoic acid.
2. Drug intermediates 3-ene hexenoic acid synthesis method according to claim 1 wherein the potassium nitrate solution has a mass fraction of 10-16%.
3. Drug intermediates 3-ene hexenoic acid synthesis method according to claim 1 wherein the mass fraction of the isopropyl butyrate solution is 30-37%.
4. Drug intermediates 3-ene hexenoic acid synthesis method according to claim 1 wherein the mass fraction of the diethyllene glycol ethereal solution is 45-52%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710529186 | 2017-07-01 | ||
| CN201710690147.1A CN108238905A (en) | 2017-07-01 | 2017-08-14 | The synthetic method of pharmaceutical intermediate 3- alkene caproic acids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IES87003B2 true IES87003B2 (en) | 2019-05-01 |
| IES20180191A2 IES20180191A2 (en) | 2019-05-01 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IES20180191A IES20180191A2 (en) | 2017-07-01 | 2018-06-26 | Drug intermediates 3-ene hexenoic acid synthesis method |
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| Country | Link |
|---|---|
| CN (1) | CN108238905A (en) |
| AU (1) | AU2018100823A4 (en) |
| IE (1) | IES20180191A2 (en) |
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2017
- 2017-08-14 CN CN201710690147.1A patent/CN108238905A/en active Pending
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2018
- 2018-06-19 AU AU2018100823A patent/AU2018100823A4/en not_active Ceased
- 2018-06-26 IE IES20180191A patent/IES20180191A2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN108238905A (en) | 2018-07-03 |
| AU2018100823A4 (en) | 2018-08-09 |
| IES20180191A2 (en) | 2019-05-01 |
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