CN104447476B - A kind of preparation method of process of sultopride hydrochloride - Google Patents
A kind of preparation method of process of sultopride hydrochloride Download PDFInfo
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- CN104447476B CN104447476B CN201410689244.5A CN201410689244A CN104447476B CN 104447476 B CN104447476 B CN 104447476B CN 201410689244 A CN201410689244 A CN 201410689244A CN 104447476 B CN104447476 B CN 104447476B
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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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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The invention discloses a kind of preparation method of process of sultopride hydrochloride; 2-methoxyl group-5-ethylsulfonyl methyl benzoate and N-ethyl-2 aminomethyl tetrahydro pyrrolidine are carried out to synthetic reaction and make process of sultopride hydrochloride crude product, last crude product refining obtains process of sultopride hydrochloride product. Process of sultopride hydrochloride quality prepared by the present invention is good, and purity is high, and preparation method is simple, less energy consumption, and cost is low.
Description
Technical field
The present invention relates to medicine and manufacture field, specifically a kind of preparation method of process of sultopride hydrochloride.
Background technology
Process of sultopride hydrochloride, chemical name: N-[(1-ethyl-2-pyrrolidinyl) methyl]-5-(ethylsulfonyl)-2-methoxyl group-benzamide hydrochloride salt, molecular formula: C17H26N2O4SHCl, molecular weight: 390.93. Process of sultopride hydrochloride has the anti-dopamine effect of maincenter. Acting on d2 dopamine receptor, is dopamine receptor-blocking agent. Its sedation is strong compared with Sulpiride, and manic, illusion, vain hope and psychomotor excitement are had to inhibitory action. This product has compared with chlorpromazine, haloperole and lithium that speed of action is fast, strong, toxic and side effect is little, therefore have feature controlling acute mental excitation state aspect.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of preparation method of process of sultopride hydrochloride, and its cost is low, and yield is high.
Technical scheme of the present invention is:
A preparation method for process of sultopride hydrochloride, comprises the steps:
(1), first 2-methoxyl group-5-ethylsulfonyl methyl benzoate and N-ethyl-2 aminomethyl tetrahydro pyrrolidine are joined in reaction vessel, and then ethylene glycol is joined in reaction vessel and heats up and stir under nitrogen protection, at 90-95 DEG C, react 10 hours, after reaction finishes, reactant liquor is added water and stirs and be cooled between 20-30 DEG C, layering, organic layer normal pressure is concentrated, add ethanol in concentrate after, normal pressure is concentrated again, finally regulate PH to 1, be cooled to 0--5 DEG C, stirring and crystallizing, centrifugal, washing, obtain wet product, wet product is through vacuum drying, vacuum cooled is to normal temperature, obtain the dry crude product of process of sultopride hydrochloride,
(2) the dry crude product of process of sultopride hydrochloride and the absolute ethyl alcohol that, step (1) are obtained, intensification is stirred to completely dissolves, add active carbon, be heated to reflux, after backflow 20-30 minute, suction filtration while hot, filtrate keeps centrifugal after 1 hour, vacuum drying, vacuum cooled to take out to normal temperature at 0-5 DEG C, obtains dry process of sultopride hydrochloride product.
The mass ratio of 2-methoxyl group-5-ethylsulfonyl methyl benzoate, N-ethyl-2 aminomethyl tetrahydro pyrrolidine and ethylene glycol in described step (1) reaction vessel is 1:0.55-1.65:0.9-1.1.
The concrete steps of the layering in described step (1) are to add carrene, jolting, standing 15min, separate organic layer, in water layer, continue to add carrene again, jolting, leave standstill 15min, separate organic layer, the organic layer separating for above-mentioned twice is merged, add water agitator treating, leave standstill, separate organic layer.
Ethanol in described step (1) is absolute ethyl alcohol or refining ethanol mother liquor.
In described step (1), regulating PH to select mass percent is 37% concentrated hydrochloric acid.
The mass ratio of the dry crude product of process of sultopride hydrochloride, absolute ethyl alcohol and active carbon in described step (2) is 1:6.3-6.4:0.04-0.06.
Advantage of the present invention:
Process of sultopride hydrochloride quality prepared by the present invention is good, and purity is high, and preparation method is simple, less energy consumption, and cost is low.
Detailed description of the invention
A preparation method for process of sultopride hydrochloride, is characterized in that, comprises the steps:
(1), first 100g2-methoxyl group-5-ethylsulfonyl methyl benzoate and 60gN-ethyl-2 aminomethyl tetrahydro pyrrolidine are joined in reaction vessel, and then 100g ethylene glycol is joined in reaction vessel and heats up and stir under nitrogen protection, at 90-95 DEG C, react 10 hours, after reaction finishes, reactant liquor is added to 500mL water to be stirred 15min and is cooled between 20-30 DEG C, add 150mL carrene, jolting, leave standstill 15min, separate organic layer, in water layer, continue to add 150mL carrene again, jolting, leave standstill 15min, separate organic layer, the organic layer separating for above-mentioned twice is merged, add 500ml water agitator treating 30min, leave standstill 30min, separate organic layer, organic layer normal pressure is concentrated, add 1050ml absolute ethyl alcohol or refining ethanol mother liquor in concentrate after, normal pressure is concentrated again, finally splashing into mass percent is that 37% concentrated hydrochloric acid regulates PH to 1, dropwise stirring at normal temperature 5-10 minute, be cooled to 0--5 DEG C, stirring and crystallizing 30min, centrifugal, use 50ml absolute ethanol washing, obtain wet product, wet product was through 60 DEG C of vacuum drying 8 hours, vacuum cooled is to normal temperature, obtain the dry crude product of process of sultopride hydrochloride,
(2), by dry 150g process of sultopride hydrochloride crude product and 1200mL absolute ethyl alcohol, intensification is stirred to completely dissolves, and adds 7.5g active carbon (added before boiling, otherwise can cause bumping), be heated to reflux, after backflow 20-30 minute, suction filtration while hot, filtrate keeps centrifugal after 1 hour, 60 DEG C of vacuum drying 8h, vacuum cooled to take out to normal temperature at 0-5 DEG C, must do process of sultopride hydrochloride product, output is about 139.5g, yield 93%, and light transmittance is more than 90%.
Claims (6)
1. a preparation method for process of sultopride hydrochloride, is characterized in that, comprises the steps:
(1), first 2-methoxyl group-5-ethylsulfonyl methyl benzoate and N-ethyl-2 aminomethyl tetrahydro pyrrolidine are joined in reaction vessel, and then ethylene glycol is joined in reaction vessel and heats up and stir under nitrogen protection, at 90-95 DEG C, react 10 hours, after reaction finishes, reactant liquor is added water and stirs and be cooled between 20-30 DEG C, layering, organic layer normal pressure is concentrated, add ethanol in concentrate after, normal pressure is concentrated again, finally regulate pH to 1, be cooled to 0--5 DEG C, stirring and crystallizing, centrifugal, washing, obtain wet product, wet product is through vacuum drying, vacuum cooled is to normal temperature, obtain the dry crude product of process of sultopride hydrochloride,
(2) the dry crude product of process of sultopride hydrochloride and the absolute ethyl alcohol that, step (1) are obtained, intensification is stirred to completely dissolves, add active carbon, be heated to reflux, after backflow 20-30 minute, suction filtration while hot, filtrate keeps centrifugal after 1 hour, vacuum drying, vacuum cooled to take out to normal temperature at 0-5 DEG C, obtains dry process of sultopride hydrochloride product.
2. the preparation method of a kind of process of sultopride hydrochloride according to claim 1, is characterized in that: the mass ratio of 2-methoxyl group-5-ethylsulfonyl methyl benzoate, N-ethyl-2 aminomethyl tetrahydro pyrrolidine and ethylene glycol in described step (1) reaction vessel is 1:0.55-1.65:0.9-1.1.
3. the preparation method of a kind of process of sultopride hydrochloride according to claim 1, it is characterized in that: the concrete steps of the layering in described step (1) are to add carrene, jolting, standing 15min, separate organic layer, then continue to add carrene in water layer, jolting, standing 15min, separate organic layer, the organic layer separating for above-mentioned twice is merged, add water agitator treating, leave standstill, separate organic layer.
4. the preparation method of a kind of process of sultopride hydrochloride according to claim 1, is characterized in that: the ethanol in described step (1) is absolute ethyl alcohol or refining ethanol mother liquor.
5. the preparation method of a kind of process of sultopride hydrochloride according to claim 1, is characterized in that: in described step (1), regulating pH to select mass percent is 37% concentrated hydrochloric acid.
6. the preparation method of a kind of process of sultopride hydrochloride according to claim 1, is characterized in that: the mass ratio of the dry crude product of process of sultopride hydrochloride, absolute ethyl alcohol and active carbon in described step (2) is 1:6.3-6.4:0.04-0.06.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410689244.5A CN104447476B (en) | 2014-11-26 | 2014-11-26 | A kind of preparation method of process of sultopride hydrochloride |
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| CN201410689244.5A CN104447476B (en) | 2014-11-26 | 2014-11-26 | A kind of preparation method of process of sultopride hydrochloride |
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| CN104447476A CN104447476A (en) | 2015-03-25 |
| CN104447476B true CN104447476B (en) | 2016-05-11 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1706825A (en) * | 2005-04-08 | 2005-12-14 | 江苏天士力帝益药业有限公司 | New synthesis process of sultopride hydrochloride |
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- 2014-11-26 CN CN201410689244.5A patent/CN104447476B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1706825A (en) * | 2005-04-08 | 2005-12-14 | 江苏天士力帝益药业有限公司 | New synthesis process of sultopride hydrochloride |
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