CN107382750A - A kind of preparation method of isoproterenol sulfate - Google Patents
A kind of preparation method of isoproterenol sulfate Download PDFInfo
- Publication number
- CN107382750A CN107382750A CN201710487481.7A CN201710487481A CN107382750A CN 107382750 A CN107382750 A CN 107382750A CN 201710487481 A CN201710487481 A CN 201710487481A CN 107382750 A CN107382750 A CN 107382750A
- Authority
- CN
- China
- Prior art keywords
- isoprel
- isoproterenol sulfate
- preparation
- ketoboidies
- methanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of preparation method of isoproterenol sulfate, comprise the following steps：（1）At room temperature, isoprel ketoboidies obtains isoprel in the solvent of methanol with hydrogenated reduction under sodium borohydride effect；（2）Negative pressure has concentrated solvent methanol, adds water and then is extracted with ethyl acetate, and adjusts system pH to be warming up to 30 minutes dissolved clarifications of backflow afterwards to acidity with 60% sulfuric acid；（3）Freeze overnight, obtain white powder crystallization；（4）Filtering, is dried, then obtain isoproterenol sulfate with ethyl alcohol recrystallization after washing；The present invention has evaded the dangerous hidden danger of high-pressure hydrogenation, makes reaction safer using sodium borohydride reduction；Using synthesis under normal pressure, avoid using metal high voltage reactor；Raw material is easy to get, technique advantages of simple.
Description
Technical field
The present invention relates to a kind of environment-friendly preparation method thereof of isoproterenol sulfate, belong to field of medicaments.
Background technology
Isoproterenol sulfate, No. CAS：299-95-6, English name：Isoproterenol Sulfate
Dihydrate, molecular formula：C22H34N2O6 H2SO4 2H2O, chemical name：4- [(2- isopropylamino -1- hydroxyls) ethyl] -
1,2- benzenediol sulfate dihydrates.Isoprel medicine is mainly used in treating bronchial astehma, is roared suitable for control
Acute attack is breathed heavily, normal aerosol inhalation, effect is fast and strong, but duration section.Heart arrest, for treating a variety of causes such as
Cardiac arrest caused by drowned, electric shock, operation accident and drug poisoning etc..If necessary can be mixed with norepinephrine.Chamber
Block.Hemorrhagic shock, available for cardiogenic shock and infectious shock.Its chemical structural formula is as follows：
Production isoproterenol sulfate mainly takes following reaction scheme at present：
The aqueous solution of isoprel ketoboidies sulfate is under palladium carbon effect after catalytic hydrogenating reduction again after a series of
Processing obtains isoproterenol sulfate.Need to use palladium-carbon catalyst in this route, palladium-carbon catalyst easily spontaneous combustion also pole
Easy in inactivation is poisoned, and simultaneous reactions need to keep Hydrogen Vapor Pressure potential safety hazard to be in use present in 0.3-0.6MPa.And
The isoproterenol sulfate aqueous solution can not contact with metal, otherwise easily lose activity.In summary, no matter from security
Or product quality stability considers the catalytic hydrogenation synthesis isoproterenol sulfate in high-pressure metal reactor
Technique is not very science, not very rational.
The content of the invention
The purpose of the present invention aiming at it is existing the defects of, there is provided a kind of technique is simple, safety and environmental protection and is easy to actual behaviour
The isoproterenol sulfate green synthesis process of work.
Present invention synthesis isoproterenol sulfate reaction equation is as follows：
Realize that the object of the invention is adopted the technical scheme that：
A kind of preparation method of isoproterenol sulfate, mainly comprises the following steps：
（1）At room temperature, isoprel ketoboidies obtains in the solvent of methanol with hydrogenated reduction under sodium borohydride effect
Isoprel；
（2）Negative pressure has concentrated solvent methanol, adds water and then is extracted with ethyl acetate, and system pH is adjusted to acid with 60% sulfuric acid
Property, 30 minutes dissolved clarifications of backflow are warming up to afterwards；
（3）Freeze overnight, obtain white powder crystallization；
（4）Filtering, is dried, then obtain isoproterenol sulfate with ethyl alcohol recrystallization after washing.
Preferably, the step as the present invention（1）In, the mol ratio of sodium borohydride and isoprel ketoboidies is 4-
10:1。
Preferably, the step as the present invention（2）In, isoprel ketoboidies is dissolved in methanol, solvent methanol with it is different
The mass ratio of third adrenaline ketoboidies is 8-15:1；
Preferably, the step as the present invention（2）In, extract selects ethyl acetate, ethyl acetate and isoprel
The mass ratio of ketoboidies is 4-8:1；
Preferably, the step as the present invention（4）In, the temperature of drying is 25-40 DEG C；The time of drying is 2-5 hours.
Preferably, the step as the present invention（2）In, tune pH value is 1-3.
The positive effect of the present invention is：（1）The dangerous hidden danger of high-pressure hydrogenation is evaded, reaction is made using sodium borohydride reduction
It is safer.（2）Using synthesis under normal pressure, avoid using metal high voltage reactor, so as to evade isoproterenol sulfate
The aqueous solution contacts with metal, deactivated possibility.（3）Raw material is easy to get, technique advantages of simple.With existing traditional production technology
Compare, the present invention has obviously economic benefit and environmental benefit.
Embodiment
Using embodiment, the present invention is further illustrated below.
Embodiment 1
Isoprel ketoboidies is added in the four-hole boiling flask exported with mechanical agitation, thermometer, air guide（94.1g,
0.45mol）, methanol 750g mix, sodium borohydride is added portionwise at 25 DEG C（69.6g 1.8mol）, add sodium borohydride it
2 hours are incubated afterwards, reaction adds deionized water 1000g, uses ethyl acetate（2×400g）, combined ethyl acetate layer.With 60% sulphur
Acid adjusts system pH to be warming up to 30 minutes dissolved clarifications of backflow afterwards to 2.Freeze overnight afterwards, obtain white powder crystallization.Filtering,
Dried after washing, then isoprenaline hydrochloride (102.7g, 0.369mol), yield 82.0% are obtained with ethyl alcohol recrystallization.
Embodiment 2
Isoprel ketoboidies is added in the four-hole boiling flask exported with mechanical agitation, thermometer, air guide（94.1g,
0.45mol）, methanol 940g mix, sodium borohydride is added portionwise at 25 DEG C（104.4g, 2.7mol）, add sodium borohydride
3 hours are incubated afterwards, reaction adds deionized water 1000g, uses ethyl acetate（2×470g）, combined ethyl acetate layer.With 60%
Sulfuric acid adjusts system pH to be warming up to 30 minutes dissolved clarifications of backflow afterwards to 3.Freeze overnight afterwards, obtain white powder crystallization.Cross
Filter, is dried, then obtain isoprenaline hydrochloride (104.3g, 0.375mol), yield 83.4% with ethyl alcohol recrystallization after washing.
Embodiment 3
Isoprel ketoboidies is added in the four-hole boiling flask exported with mechanical agitation, thermometer, air guide（94.1g,
0.45mol）, methanol 1030g mix, sodium borohydride is added portionwise at 25 DEG C（121.8g, 3.15mol）, add hydroboration
4 hours are incubated after sodium, reaction adds deionized water 1000g, uses ethyl acetate（2×560g）, combined ethyl acetate layer.With
60% sulfuric acid adjusts system pH to be warming up to 30 minutes dissolved clarifications of backflow afterwards to 1.5.Freeze overnight afterwards, obtain white powder knot
It is brilliant.Filtering, is dried, then obtain isoprenaline hydrochloride (104.8g, 0.377mol), yield with ethyl alcohol recrystallization after washing
83.8%。
Embodiment 4
Isoprel ketoboidies is added in the four-hole boiling flask exported with mechanical agitation, thermometer, air guide（94.1g,
0.45mol）, methanol 1200g mix, sodium borohydride is added portionwise at 25 DEG C（139.2g, 3.6mol）, add sodium borohydride
4 hours are incubated afterwards, reaction adds deionized water 1000g, uses ethyl acetate（2×650g）, combined ethyl acetate layer.With 60%
Sulfuric acid adjusts system pH to be warming up to 30 minutes dissolved clarifications of backflow afterwards to 1.Freeze overnight afterwards, obtain white powder crystallization.Cross
Filter, is dried, then obtain isoprenaline hydrochloride (105.7g, 0.380mol), yield 84.5% with ethyl alcohol recrystallization after washing.
Embodiment 5
Isoprel ketoboidies is added in the four-hole boiling flask exported with mechanical agitation, thermometer, air guide（94.1g,
0.45mol）, methanol 1400g mix, sodium borohydride is added portionwise at 25 DEG C（174.0g, 4.5mol）, add sodium borohydride
4 hours are incubated afterwards, reaction adds deionized water 1000g, uses ethyl acetate（2×750g）, combined ethyl acetate layer.With 60%
Sulfuric acid adjusts system pH to be warming up to 30 minutes dissolved clarifications of backflow afterwards to 1.8.Freeze overnight afterwards, obtain white powder crystallization.Cross
Filter, is dried, then obtain isoprenaline hydrochloride (107.2g, 0.386mol), yield 85.7% with ethyl alcohol recrystallization after washing.
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, on the premise of the technical principle of the present invention is not departed from, some improvement and modification can also be made, these improve and become
Type also should be regarded as protection scope of the present invention.
Claims (6)
1. a kind of preparation method of isoproterenol sulfate, the reaction equation of the isoproterenol sulfate are as follows：
Characterized in that, mainly comprise the following steps：
（1）At room temperature, isoprel ketoboidies obtains in the solvent of methanol with hydrogenated reduction under sodium borohydride effect
Isoprel；
（2）Negative pressure has concentrated solvent methanol, adds water and then is extracted with ethyl acetate, and system pH is adjusted to acid with 60% sulfuric acid
Property, 30 minutes dissolved clarifications of backflow are warming up to afterwards；
（3）Freeze overnight, obtain white powder crystallization；
（4）Filtering, is dried, then obtain isoproterenol sulfate with ethyl alcohol recrystallization after washing.
A kind of 2. preparation method of isoproterenol sulfate as claimed in claim 1, it is characterised in that the step
（1）In, the mol ratio of sodium borohydride and isoprel ketoboidies is 4-10:1.
A kind of 3. preparation method of isoproterenol sulfate as claimed in claim 1, it is characterised in that the step
（2）In, isoprel ketoboidies is dissolved in methanol, and the mass ratio of solvent methanol and isoprel ketoboidies is 8-15:1.
A kind of 4. preparation method of isoproterenol sulfate as claimed in claim 1, it is characterised in that the step
（2）In, extract selects ethyl acetate, and the mass ratio of ethyl acetate and isoprel ketoboidies is 4-8:1.
A kind of 5. preparation method of isoproterenol sulfate as claimed in claim 1, it is characterised in that the step
（4）In, the temperature of drying is 25-40 DEG C；The time of drying is 2-5 hours.
A kind of 6. preparation method of isoproterenol sulfate as claimed in claim 1, it is characterised in that the step
（2）In, the tune pH value is 1-3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710487481.7A CN107382750B (en) | 2017-06-23 | 2017-06-23 | A kind of preparation method of isoproterenol sulfate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710487481.7A CN107382750B (en) | 2017-06-23 | 2017-06-23 | A kind of preparation method of isoproterenol sulfate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107382750A true CN107382750A (en) | 2017-11-24 |
| CN107382750B CN107382750B (en) | 2019-09-20 |
Family
ID=60333589
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710487481.7A Active CN107382750B (en) | 2017-06-23 | 2017-06-23 | A kind of preparation method of isoproterenol sulfate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107382750B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112724027A (en) * | 2021-01-19 | 2021-04-30 | 河北坤安药业有限公司 | Preparation method of isoproterenol hydrochloride |
| CN115611750A (en) * | 2022-10-31 | 2023-01-17 | 成都新恒创药业有限公司 | Synthesis method of isoproterenol hydrochloride |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3868461A (en) * | 1972-11-22 | 1975-02-25 | Interx Research Corp | Ester of 3,4-dihydroxy-alpha (isopropylamino) methyl benzyl alcohol, composition and anti-asthma use thereof |
| US20060078707A1 (en) * | 2002-06-17 | 2006-04-13 | Selinfreund Richard H | Changing light absorption by disruption of conjugation |
| WO2007082239A2 (en) * | 2006-01-10 | 2007-07-19 | Verification Technologies, Inc. | Data-protected digital recording medium |
-
2017
- 2017-06-23 CN CN201710487481.7A patent/CN107382750B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3868461A (en) * | 1972-11-22 | 1975-02-25 | Interx Research Corp | Ester of 3,4-dihydroxy-alpha (isopropylamino) methyl benzyl alcohol, composition and anti-asthma use thereof |
| US20060078707A1 (en) * | 2002-06-17 | 2006-04-13 | Selinfreund Richard H | Changing light absorption by disruption of conjugation |
| WO2007082239A2 (en) * | 2006-01-10 | 2007-07-19 | Verification Technologies, Inc. | Data-protected digital recording medium |
Non-Patent Citations (4)
| Title |
|---|
| BEKE, D.等: "A new synthesis of N-isopropylnoradrenaline", 《PHARMAZEUTISCHE ZENTRALHALLE FUER DEUTSCHLAND》 * |
| DAVID G. AHERN等: "Tritiation of two potent catecholamine beta-adrenergic receptor agonists", 《J RADIOANAL NUCL CHEM》 * |
| FODOR, GABOR等: "A Synthesis of adrenaline-like compounds", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| 段颖: "两种拟肾上腺素药物中间体的合成研究", 《万方数据知识服务平台 学位》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112724027A (en) * | 2021-01-19 | 2021-04-30 | 河北坤安药业有限公司 | Preparation method of isoproterenol hydrochloride |
| CN112724027B (en) * | 2021-01-19 | 2022-03-01 | 河北坤安药业有限公司 | Preparation method of isoproterenol hydrochloride |
| CN115611750A (en) * | 2022-10-31 | 2023-01-17 | 成都新恒创药业有限公司 | Synthesis method of isoproterenol hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107382750B (en) | 2019-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107382750A (en) | A kind of preparation method of isoproterenol sulfate | |
| CN109651150A (en) | A method of preparing vitamine A acetate | |
| CN110156620A (en) | A kind of preparation method of tranexamic acid | |
| CN107868072A (en) | A kind of preparation method of Berberine hydrochloride intermediate | |
| CN107011188B (en) | Preparation method of isoproterenol hydrochloride | |
| CN106748906B (en) | A kind of synthetic method of bumetanide | |
| CN108863822B (en) | Method for refining isoproterenol hydrochloride | |
| CN106831503A (en) | A kind of preparation method of Terephthalidene Dicamphor Sulfonic Acid's sun-screening agent | |
| CN101024638A (en) | Technology for extracting Baicalin | |
| Querard et al. | Direct synthesis of indenes via a rhodium-catalyzed multicomponent C sp2–H annulation reaction | |
| CN104130193B (en) | A kind of synthetic method of 5-acetoacetylaminobenzimidazolone | |
| CN113042040B (en) | Method for preparing tranexamic acid by using platinum-carbon catalyst | |
| CN107880012A (en) | The synthetic method of the veratryl homopiperony lamine hydrochlorides of N 2 ', 3 ' | |
| CN109485578A (en) | The synthesis technology of 2- amino -1,3- propylene glycol | |
| CN106478433B (en) | One kind preparing the adrenergic method of raceme by S- adrenaline | |
| KR101776412B1 (en) | New benzimidazole-ruthenium derivatives and pharmaceutical composition for preventing or treating cancer comprising the same | |
| CN102532011A (en) | Method for preparing Roflumilast raw material and intermediates | |
| CN107185571B (en) | Cobalt catalyst, preparation method thereof and application thereof in catalytic synthesis of 2,3, 5-trimethylbenzoquinone | |
| CN102276484B (en) | Method for preparing 2-phenyl-4,4'-diamido diphenyl ether | |
| CN105418489A (en) | Synthesis method of bupivacaine | |
| CN106083667B (en) | A kind of synthetic method of 2 amino (4 ethylsulfonyl) phenol | |
| CN108774139A (en) | The preparation method of N- methyl paranitroanilines | |
| CN103936704A (en) | Method of preparing chrysin | |
| CN102153485B (en) | Method for preparing dipivefrine | |
| CN106986783A (en) | A kind of preparation method of 3 aminophthalic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |