AU2016102303A4 - Ketamine drug intermediates cyclopentene synthesis method - Google Patents
Ketamine drug intermediates cyclopentene synthesis method Download PDFInfo
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- AU2016102303A4 AU2016102303A4 AU2016102303A AU2016102303A AU2016102303A4 AU 2016102303 A4 AU2016102303 A4 AU 2016102303A4 AU 2016102303 A AU2016102303 A AU 2016102303A AU 2016102303 A AU2016102303 A AU 2016102303A AU 2016102303 A4 AU2016102303 A4 AU 2016102303A4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/321—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a non-metal atom
- C07C1/323—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a non-metal atom the hetero-atom being a nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C7/00—Purification; Separation; Use of additives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C7/00—Purification; Separation; Use of additives
- C07C7/10—Purification; Separation; Use of additives by extraction, i.e. purification or separation of liquid hydrocarbons with the aid of liquids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C7/00—Purification; Separation; Use of additives
- C07C7/14—Purification; Separation; Use of additives by crystallisation; Purification or separation of the crystals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
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- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Ketamine drug intermediates cyclopentene synthesis method, comprising the following steps: tubular reactor was added 1.56 mol nickel oxide, added 1.3mol cyclopentylamine (2), added 1.6-1.9mol 1-nitrotoluene solution(3), added 300ml oxalic acid solution, reaction temperature was increased to 270-280C, continued reaction for 90-120min, then raising the temperature to 300-310 C, the reaction was continued 50-70min, after the thermal cracking reaction, the reactor temperature was lowered to 20 -25 C, condensed vapor, the aqueous layer was separated, oil layer was washed with salt solution , washed with xylene solution, dehydrated with dehydrating agent, recrystallized in the acetamide solution, got crystal cyclopentene.
Description
Ketamine drug intermediates cyclopentene synthesis method TECHNICAL FIELD
The present invention relates to ketamine drug intermediates cyclopentene synthesis method.
BACKGROUND ART
Ketamine is used for variety of minor surgery or diagnostic procedures, you can use separate it anesthesia. For muscle relaxation required surgery, you can add muscle relaxant; for towing heavy visceral surgery, you can compatible with other medicines to reduce the traction reaction, it can be used for other inducers of general anesthesia and for auxiliary anesthetic properties weak anesthetic anesthesia, or in combination with other systemic or local anesthesia combined, cyclopentene as ketamine drug intermediates, its synthesis method is of great economic significance for improving drug synthesis product quality, reducing the by-product content.
SUMMARY OF THE INVENTION
Object of the present invention is to provide ketamine drug intermediates cyclopentene synthesis method, comprising the following steps: (i)tubular reactor was added 1.56 mol nickel oxide, added 1.3mol cyclopentylamine (2), added 1.6-1.9mol 1-nitrotoluene solution(3), added 300ml oxalic acid solution, reaction temperature was increased to 270-280°C, continued reaction for 90-120min, then raising the temperature to 300-310 °C, the reaction was continued 50-70min, after the thermal cracking reaction, the reactor temperature was lowered to 20 -25 °C, condensed vapor, the aqueous layer was separated, oil layer was washed with salt solution , washed with xylene solution, dehydrated with dehydrating agent, recrystallized in the acetamide solution, got crystal cyclopentene (1); wherein, nitrotoluene solution in step (i) has a mass fraction of 60-65%; oxalic acid solution in step (i) has a mass fraction of 30-35%;salt solution in step (i) is any of ammonium bromide solution or magnesium nitrate solution; xylene solution in step (i) has a mass fraction of 70-75%; dehydrating agent in step (i) is any of phosphorus pentoxide or anhydrous potassium carbonate;acetamide solution in step (i) has a mass fraction of 90-95%.
The throughout reaction process can be summarized using the following reaction formula:
Advantage of the present invention is that: the reaction intermediate links are reduced, reducing the reaction temperature and reaction time, improving the reaction yield.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
Embodiment 1
Tubular reactor was added 1.56 mol nickel oxide, added 1.3mol cyclopentylamine (2), added 1.6-1.9mol 1-nitrotoluene solution(3) with a mass fraction of 60%, added 300ml oxalic acid solution with a mass fraction of 30%, reaction temperature was increased to 270°C, continued reaction for 90min, then raising the temperature to 300 °C, the reaction was continued 50min, after the thermal cracking reaction, the reactor temperature was lowered to 20 °C, condensed vapor, the aqueous layer was separated, oil layer was washed with ammonium bromide solution , washed with xylene solution with a mass fraction of 70%, dehydrated with phosphorus pentoxide dehydrating agent, recrystallized in the acetamide solution with a mass fraction of 90%, got crystal cyclopentene 73.37 g, yield 83%.
Embodiment 2
Tubular reactor was added 1.56 mol nickel oxide, added 1.3mol cyclopentylamine (2), added 1.6-1.9mol 1-nitrotoluene solution(3) with a mass fraction of 62%, added 300ml oxalic acid solution with a mass fraction of 32%, reaction temperature was increased to 275°C, continued reaction for llOmin, then raising the temperature to 305 °C, the reaction was continued 60min, after the thermal cracking reaction, the reactor temperature was lowered to 22°C, condensed vapor, the aqueous layer was separated, oil layer was washed with magnesium nitrate solution , washed with xylene solution with a mass fraction of 72%, dehydrated with anhydrous potassium carbonate dehydrating agent, recrystallized in the acetamide solution with a mass fraction of 92%, got crystal cyclopentene 76.02 g, yield 86%.
Embodiment 3
Tubular reactor was added 1.56 mol nickel oxide, added 1.3mol cyclopentylamine (2), added 1.6-1.9mol 1-nitrotoluene solution(3) with a mass fraction of 65%, added 300ml oxalic acid solution with a mass fraction of 35%, reaction temperature was increased to 280°C, continued reaction for 120min, then raising the temperature to 310°C, the reaction was continued 70min, after the thermal cracking reaction, the reactor temperature was lowered to 25 °C, condensed vapor, the aqueous layer was separated, oil layer was washed with ammonium bromide solution , washed with xylene solution with a mass fraction of 75%, dehydrated with phosphorus pentoxide dehydrating agent, recrystallized in the acetamide solution with a mass fraction of 95%, got crystal cyclopentene 81.33 g, yield 92%.
While a number of preferred embodiments have been described, it will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
Claims (4)
1. Ketamine drug intermediates cyclopentene synthesis method,comprising the following steps: (i)tubular reactor was added 1.56 mol nickel oxide, added 1.3mol cyclopentylamine(2), added 1.6-1.9mol 1-nitrotoluene solution(3), added 300ml oxalic acid solution, reaction temperature was increased to 270-280°C, continued reaction for 90-120min, then raising the temperature to 300-310 °C, the reaction was continued 50-70min, after the thermal cracking reaction, the reactor temperature was lowered to 20 -25 °C, condensed vapor, the aqueous layer was separated, oil layer was washed with salt solution, washed with xylene solution, dehydrated with dehydrating agent, recrystallized in the acetamide solution, got crystal cyclopentene (1): wherein, nitrotoluene solution in step (i) has a mass fraction of 60-65%; oxalic acid solution in step (i) has a mass fraction of 30- 35%;salt solution in step (i) is any of ammonium bromide solution or magnesium nitrate solution.
2. Ketamine drug intermediates cyclopentene synthesis method according to claim 1 wherein xylene solution in step (i) has a mass fraction of 70-75%.
3. Ketamine drug intermediates cyclopentene synthesis method according to claim 1 wherein dehydrating agent in step (i) is any of phosphorus pentoxide or anhydrous potassium carbonate.
4. Ketamine drug intermediates cyclopentene synthesis method according to claim 1 wherein acetamide solution in step (i) has a mass fraction of 90-95%.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201511000693.5A CN105503494A (en) | 2015-12-25 | 2015-12-25 | Synthetic method for medical intermediate cyclopentene of ketamine |
| CN2015110006935 | 2015-12-25 | ||
| CN201610830870.0A CN106397086A (en) | 2015-12-25 | 2016-09-19 | Synthesis method of ketamine drug intermediate cyclopentene |
| CN2016108308700 | 2016-09-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016102303A4 true AU2016102303A4 (en) | 2017-02-23 |
Family
ID=55711872
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016102303A Ceased AU2016102303A4 (en) | 2015-12-25 | 2016-12-24 | Ketamine drug intermediates cyclopentene synthesis method |
Country Status (2)
| Country | Link |
|---|---|
| CN (2) | CN105503494A (en) |
| AU (1) | AU2016102303A4 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112194602A (en) * | 2020-03-17 | 2021-01-08 | 国药集团工业有限公司 | Synthesis method of ketamine and its derivatives and intermediates |
-
2015
- 2015-12-25 CN CN201511000693.5A patent/CN105503494A/en active Pending
-
2016
- 2016-09-19 CN CN201610830870.0A patent/CN106397086A/en active Pending
- 2016-12-24 AU AU2016102303A patent/AU2016102303A4/en not_active Ceased
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112194602A (en) * | 2020-03-17 | 2021-01-08 | 国药集团工业有限公司 | Synthesis method of ketamine and its derivatives and intermediates |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105503494A (en) | 2016-04-20 |
| CN106397086A (en) | 2017-02-15 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |