CN104447477A - Method for preparing sulpiride - Google Patents
Method for preparing sulpiride Download PDFInfo
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- CN104447477A CN104447477A CN201410713872.2A CN201410713872A CN104447477A CN 104447477 A CN104447477 A CN 104447477A CN 201410713872 A CN201410713872 A CN 201410713872A CN 104447477 A CN104447477 A CN 104447477A
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- sulpiride
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- filter cake
- suction filtration
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for preparing sulpiride. The method comprises the following steps: firstly, carrying out condensation reaction on 2-methoxy-5-aminosulfanoyl methyl benzoate and N-ethyl-2-aminomethyl tetrahydropyrrole to generate a crude sulpiride product; and refining the crude sulpiride product to obtain a refined sulpiride product. The sulpiride prepared by the method has the advantages of good quality, high purity, simple preparation method, low energy consumption and low cost.
Description
Technical field
The present invention relates to medicine and manufacture field, specifically a kind of preparation method of Sulpiride.
Background technology
Sulpiride, chemical name N-(1-ethyl-pyrolidine-2-base-methyl)-2-methoxyl group-5-sulphonamide-benzamide, belongs to antipsychotic drug.Indication: to indifferent, shrink back, the effect of numb, depressed, illusion and vain hope symptom is better, be applicable to schizophrenia simple type, intolerance style, catatonic type and chronic schizophrenia unsociable and eccentric, shrink back, indifferent symptom.Certain curative effect is had to depressive symptom.Other purposes have preventing or arresting vomiting.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of preparation method of Sulpiride, and its preparation method is simple, and yield is high.
Technical scheme of the present invention is:
A preparation method for Sulpiride, is characterized in that: comprise the steps:
(1), first 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters and N-ethyl-2 aminomethyl tetrahydro pyrrolidine are joined in reaction vessel, and then drop into glycerine, heat up stirring under nitrogen protection, react 10 hours at 90-95 DEG C, after reaction terminates, add water stirring, be cooled to 20-30 DEG C of stoppings and pass into nitrogen, ice bath cooling keeps filtering for 30 minutes at 0-5 DEG C, and filter cake washing, vacuum-drying, obtain Sulpiride crude product;
(2), the Sulpiride crude product that step (1) is obtained is joined stirring heating in reaction vessel together with methyl alcohol, hydrochloric acid is dripped at 60-65 DEG C, dropping terminates rear insulation 1h, then cool to 5-10 DEG C insulation 30min after suction filtration, again filter cake is joined in the mixed solution of first alcohol and water, heat temperature raising makes filter cake dissolve, add gac, be heated to backflow 20min, suction filtration, then mother liquor is warmed up to 60-65 DEG C of adjustment pH to 9.8-10.1, finally cool to 0-5 DEG C of insulation 30min, suction filtration, vacuum-drying, obtain Sulpiride fine work.
In described step (1), the mass ratio of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters and N-ethyl-2 aminomethyl tetrahydro pyrrolidine is 1: 0.52-0.53.
PH is regulated to select potassium hydroxide solution in described step (2).
Advantage of the present invention:
Sulpiride quality prepared by the present invention is good, and purity is high, and preparation method is simple, and less energy consumption, cost is low.
Embodiment
A preparation method for Sulpiride, is characterized in that: comprise the steps:
(1), first 98.4g 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters and 51.2g N-ethyl-2 aminomethyl tetrahydro pyrrolidine are joined in reaction vessel, and then drop into 180ml glycerine, heat up stirring under nitrogen protection, react 10 hours at 90-95 DEG C, after reaction terminates, add 300ml water and stir, be cooled to 20-30 DEG C of stoppings and pass into nitrogen, ice bath cooling keeps filtering for 30 minutes at 0-5 DEG C, and filter cake washing, vacuum-drying at 60 DEG C, obtain Sulpiride crude product;
(2), 112g Sulpiride crude product is joined stirring heating in reaction vessel together with 450ml methyl alcohol, the hydrochloric acid that 31ml regulates per-cent 37% is dripped at 60-65 DEG C, dropping terminates rear insulation 1h, then cool to 5-10 DEG C insulation 30min after suction filtration, again filter cake is joined in the mixed solution of 215ml methyl alcohol and 270ml water, heat temperature raising makes filter cake dissolve, add 3g gac, be heated to backflow 20min, suction filtration, again mother liquor is warmed up to 60-65 DEG C of potassium hydroxide solutions by mass percent 30% and regulates pH to 9.8-10.1, finally cool to 0-5 DEG C of insulation 30min, suction filtration, vacuum-drying at 60 DEG C, obtain Sulpiride fine work, yield 88.4%.
Claims (3)
1. a preparation method for Sulpiride, is characterized in that: comprise the steps:
(1), first 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters and N-ethyl-2 aminomethyl tetrahydro pyrrolidine are joined in reaction vessel, and then drop into glycerine, heat up stirring under nitrogen protection, react 10 hours at 90-95 DEG C, after reaction terminates, add water stirring, be cooled to 20-30 DEG C of stoppings and pass into nitrogen, ice bath cooling keeps filtering for 30 minutes at 0-5 DEG C, and filter cake washing, vacuum-drying, obtain Sulpiride crude product;
(2), the Sulpiride crude product that step (1) is obtained is joined stirring heating in reaction vessel together with methyl alcohol, hydrochloric acid is dripped at 60-65 DEG C, dropping terminates rear insulation 1h, then cool to 5-10 DEG C insulation 30min after suction filtration, again filter cake is joined in the mixed solution of first alcohol and water, heat temperature raising makes filter cake dissolve, add gac, be heated to backflow 20min, suction filtration, then mother liquor is warmed up to 60-65 DEG C of adjustment pH to 9.8-10.1, finally cool to 0-5 DEG C of insulation 30min, suction filtration, vacuum-drying, obtain Sulpiride fine work.
2. the preparation method of a kind of Sulpiride according to claim 1, is characterized in that: in described step (1), the mass ratio of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters and N-ethyl-2 aminomethyl tetrahydro pyrrolidine is 1: 0.52-0.53.
3. the preparation method of a kind of Sulpiride according to claim 1, is characterized in that: regulate pH to select potassium hydroxide solution in described step (2).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410713872.2A CN104447477B (en) | 2014-12-02 | 2014-12-02 | A kind of preparation method of Sulpiride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410713872.2A CN104447477B (en) | 2014-12-02 | 2014-12-02 | A kind of preparation method of Sulpiride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104447477A true CN104447477A (en) | 2015-03-25 |
| CN104447477B CN104447477B (en) | 2016-05-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410713872.2A Expired - Fee Related CN104447477B (en) | 2014-12-02 | 2014-12-02 | A kind of preparation method of Sulpiride |
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| CN (1) | CN104447477B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105481733A (en) * | 2015-12-30 | 2016-04-13 | 苏州诚和医药化学有限公司 | Method for synthesizing 2-methoxy-5-aminosulfonylmethyl benzoate by one-step method |
| CN108341765A (en) * | 2018-04-10 | 2018-07-31 | 大桐制药（中国）有限责任公司 | A kind of preparation method of the high-purity Sulpiride of environmental protection |
| CN112441960A (en) * | 2020-12-14 | 2021-03-05 | 常州康普药业有限公司 | Synthetic method of sulpiride |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772256A (en) * | 2012-10-24 | 2014-05-07 | 天士力控股集团有限公司 | Preparation method for high-purity sulpiride or optical isomers thereof |
| CN103804265A (en) * | 2012-11-08 | 2014-05-21 | 江苏天士力帝益药业有限公司 | Synthesis and post-processing method of sulpiride or optical isomer thereof |
-
2014
- 2014-12-02 CN CN201410713872.2A patent/CN104447477B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772256A (en) * | 2012-10-24 | 2014-05-07 | 天士力控股集团有限公司 | Preparation method for high-purity sulpiride or optical isomers thereof |
| CN103804265A (en) * | 2012-11-08 | 2014-05-21 | 江苏天士力帝益药业有限公司 | Synthesis and post-processing method of sulpiride or optical isomer thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105481733A (en) * | 2015-12-30 | 2016-04-13 | 苏州诚和医药化学有限公司 | Method for synthesizing 2-methoxy-5-aminosulfonylmethyl benzoate by one-step method |
| CN108341765A (en) * | 2018-04-10 | 2018-07-31 | 大桐制药（中国）有限责任公司 | A kind of preparation method of the high-purity Sulpiride of environmental protection |
| CN112441960A (en) * | 2020-12-14 | 2021-03-05 | 常州康普药业有限公司 | Synthetic method of sulpiride |
| CN112441960B (en) * | 2020-12-14 | 2022-03-01 | 常州康普药业有限公司 | Synthetic method of sulpiride |
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| CN104447477B (en) | 2016-05-11 |
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| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhang Yanhua Inventor after: Zhang Yuan Inventor before: Yang Huilai Inventor before: Mao Jie Inventor before: Sun Xuexi |
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| COR | Change of bibliographic data | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20161021 Address after: 230000 Anhui city of Hefei Province Economic and Technological Development Zone Qi Yun Road No. 1 Patentee after: DATONG PHARMACEUTICAL (CHINA) CO.,LTD. Address before: 230601 Anhui Province, Hefei City Economic Development Zone, two private technology park green Luan Road No. 8 Patentee before: CHEER FINE PHARMACEUTICAL(ANHUI) CO.,LTD. |
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| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160511 Termination date: 20211202 |