CN1267664A - Preparation of levorotary alpha-methylamino phenyl acetone - Google Patents
Preparation of levorotary alpha-methylamino phenyl acetone Download PDFInfo
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- CN1267664A CN1267664A CN 00103440 CN00103440A CN1267664A CN 1267664 A CN1267664 A CN 1267664A CN 00103440 CN00103440 CN 00103440 CN 00103440 A CN00103440 A CN 00103440A CN 1267664 A CN1267664 A CN 1267664A
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- methylephedrone
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Abstract
In the present invention, various levorotary comphorsulfonic acid and its bromide is used to separate racemic metamfepyramone in water as solvent to obtain levorotary metamfepyramone salt, which is dissolved in water and mixed with isoequivalent ammonia water or barium hydrochloride and organic solvent to obtain levorotary metamfepyramone from organic solvent with the mother liquor being mixed with sulfuric acid to eliminate inorganic salt. The mother liquor after separation is mixed with isoequivalent ammonia water or barium hydrochloride, heated to racemize, mixed with iso-equivalent sulfuric acid and filtered to eliminate inorganic salt, cooled to crystallize and separate levorotary metamfepyramone; or the mother liquor is heated directly to racemize in the protection of acid and cooled to crystallize and separate levorotary metamfepyramone salt.
Description
The invention belongs to the preparation method of medicine intermediate.Left-handed α-N-methylephedrone is the important intermediate of the left-handed α of preparation medical material-methylamine phenylpropyl alcohol.
Fractionation about the racemize N-methylephedrone is adopted as the dextrorotation Tartaric acid always, and d-camphorsulfonic acid is made resolving agent.In order to obtain left-handed α-N-methylephedrone, must with an organic solvent make resolution solvent, as methyl alcohol, ethanol, propyl alcohol, butanols etc., to report for work for No. 639126 as German Patent, English Patent is reported for work for No. 768772, and yield is not high.Use a large amount of organic solvents in process of production, production cost height, deficiency in economic performance.And resolving agent does not have effectively economic method to carry out the recirculation use.
The objective of the invention is to adopt left-handed camphor-10-sulfonic acid, left-handed 3-bromo-camphor-10-sulfonic acid, left-handed camphor-8-sulfonic acid, left-handed 3-bromo-camphor-8-sulfonic acid, left-handed dextrocamphoric acid is made the resolving agent of α-N-methylephedrone, can in water, effectively split, and the yield height.Fractionation obtains the mother liquor of α-left-handed N-methylephedrone; can directly add above-mentioned various acid or mineral acid sulfuric acid; hydrochloric acid is made protective material; direct heating racemization under acidic conditions, crystallisation by cooling can obtain α-left-handed N-methylephedrone again then, or mother liquor is added aqua ammonia or hydrated barta; heat racemization then; add sulfuric acid or hydrochloric acid after finishing again, remove by filter ammonium sulfate or ammonium chloride or barium sulfate, the mother liquor cooling can obtain α-left-handed N-methylephedrone again.
The present invention be with the racemize N-methylephedrone with the left-handed camphor of equivalent-10-sulfonic acid or left-handed 3-bromo-camphor-10-sulfonic acid or left-handed camphor-8-sulfonic acid, left-handed-3-bromo-camphor-8-sulfonic acid, left-handed dextrocamphoric acid.Be dissolved in certain water gaging heating for dissolving, crystallisation by cooling; obtain left-handed N-methylephedrone camsilate, mother liquor adds a certain amount of acid to be protected, and racemization is carried out in heating; crystallisation by cooling; can obtain left-handed N-methylephedrone camsilate again, or directly add the aqua ammonia or the hydrogen-oxygen barium of equivalent in mother liquor, racemization is carried out in heating; and then add the sulfuric acid or the hydrochloric acid of above-mentioned alkali equivalent; remove inorganic salt, mother liquor further cools off, and another obtains left-handed N-methylephedrone camsilate.The horizontal hydrochlorate of left-handed N-methylephedrone camphor that obtains is soluble in water, and the ammoniacal liquor or the hydrogen chlorine water barium of adding equivalent separate obtaining left-handed N-methylephedrone.Mother liquor adds the sulfuric acid or the hydrochloric acid of equivalent, is concentrated to a certain degree, removes by filter inorganic salt, ammonium sulfate or barium sulfate, and mother liquor is l-camphor sulfonic acid solution, and is reusable.
Prepare left-handed N-methylephedrone with method of the present invention,, can make to use water as resolution solvent owing to adopt l-camphor sulfonic acid to make resolving agent, economical and practical, and resolving agent can conveniently be reused economically feasible.
Further specified the present invention in order to illustrate better below by embodiment.
Embodiment 1:
32.6g racemize methylamine acetone and the left-handed sulphur brain of 46.4g-10-sulfonic acid are dissolved in the 95ml water, heating for dissolving, crystallisation by cooling splits out left-handed N-methylephedrone salt, filtering separation gets 35.5g salt, resolution yield 90%, specific rotatory power [α]=-34.2 is dissolved in this salt in the 100ml water, add concentration 10% ammoniacal liquor 31.5g, with the left-handed N-methylephedrone of methylbenzene extraction, pressure reducing and steaming toluene obtains the 14.6g N-methylephedrone.Add concentration 20% sulfuric acid 22.05g in the mother liquor, concentrating under reduced pressure to moisture be 100% concentration, cool to room temperature removes by filter inorganic salt ammonium sulfate, mother liquor is the l-camphor sulfonic acid aqueous solution, is used to recycle.
Mother liquor behind the left-handed N-methylephedrone of above-mentioned crystallization is added 2 gram left-handed camphor-10-sulfonic acid, heat to 130 degree, 5 hours time, crystallisation by cooling then, another splits out left-handed N-methylephedrone 18.6g, specific rotatory power [α]=-30.2, mother liquor can repeat to heat racemization, and cooling splits out left-handed N-methylephedrone salt.
Example 2,32.6g racemize N-methylephedrone and the left-handed camphor of 46.4g-8-sulfonic acid are dissolved in the 90ml water, the heating for dissolving crystallisation by cooling, split out left-handed N-methylephedrone salt, filtering separation gets 32.4g salt, resolution yield 88%, specific rotatory power [α]=-30.8 degree, this salt is dissolved in the 100ml water, adds hydrochlorinate barium 7.28g, with the left-handed N-methylephedrone of methylbenzene extraction, adding concentration in the mother liquor is 20% sulfuric acid 22.05g, remove by filter inorganic salt barium sulfate, mother liquor is left-handed camphor-8-sulfonate aqueous solution, is used to recycle.
With the mother liquor that splits out once after the left-handed N-methylephedrone salt, adding concentration is 10% ammoniacal liquor 38.4g, is heated to 35 degree, and 24 hours time, adding concentration then is 20% sulfuric acid 28.9g; Then concentrating under reduced pressure to moisture be 120% concentration, be cooled to 25 degree, remove by filter inorganic salt ammonium sulfate, further be cooled to zero degree, crystallization goes out left-handed N-methylephedrone salt 14.7g, specific rotatory power [α]=-29.4 degree.
Claims (4)
1, a kind of preparation method of left-handed α-N-methylephedrone, α-N-methylephedrone is
,, left-handed-3-bromo-camphor-10-sulfonic acid with left-handed camphor-10-sulfonic acid, left-handed camphor-8-sulfonic acid, left-handed 3-bromo-camphor-8-sulfonic acid, left-handed dextrocamphoric acid is made resolving agent, makes resolution solvent with water, the resolution of racemic N-methylephedrone, heating for dissolving, crystallisation by cooling gets left-handed N-methylephedrone salt.
It is 2, according to claim 1 that will to split the left-handed N-methylephedrone salt of gained soluble in water, after carrying out hydrogenating reduction by usual way, to ammoniacal liquor that wherein adds equivalent or hydrated barta, use the left-handed methylamine phenylpropyl alcohol of organic solvent extraction then, mother liquor adds the sulfuric acid or the hydrochloric acid of equivalent, concentrates and removes a certain amount of water, remove by filter inorganic salt, ammonium sulfate or ammonium chloride or barium sulfate, mother liquor are the above-mentioned all kinds of l-camphor sulfonic acid aqueous solution, are used to recycle.
3, according to claim 1, it is mother liquid obtained to split the back, adds a certain amount of above-mentioned all kinds of acid or mineral acid sulfuric acid, and hydrochloric acid, pH value are below 7, and racemization is carried out in heating, and temperature is between 50 degree-200 degree.After isoracemization was finished, crystallisation by cooling can get left-handed N-methylephedrone salt.
4, the ammoniacal liquor or the hydrated barta that will split the mother liquid obtained adding equivalent in back according to claim 1, the heating racemization, temperature is between the 10-80 degree, after treating that racemization is finished, add the sulfuric acid or the hydrochloric acid of ammoniacal liquor or hydrated barta equivalent, remove by filter inorganic salt barium sulfate, or ammonium sulfate or ammonium chloride, mother liquor is cooled to the 0-10 degree, can get left-handed N-methylephedrone salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00103440 CN1267664A (en) | 2000-03-14 | 2000-03-14 | Preparation of levorotary alpha-methylamino phenyl acetone |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 00103440 CN1267664A (en) | 2000-03-14 | 2000-03-14 | Preparation of levorotary alpha-methylamino phenyl acetone |
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| CN1267664A true CN1267664A (en) | 2000-09-27 |
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| CN 00103440 Pending CN1267664A (en) | 2000-03-14 | 2000-03-14 | Preparation of levorotary alpha-methylamino phenyl acetone |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005118524A1 (en) * | 2004-06-02 | 2005-12-15 | Shanghai Institute Of Pharmaceutical Industry | Process for preparing [(s)-(-)alpha-methylamino phenylacetone]2 (2r, 3r)-tartaric acid derivates |
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2000
- 2000-03-14 CN CN 00103440 patent/CN1267664A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005118524A1 (en) * | 2004-06-02 | 2005-12-15 | Shanghai Institute Of Pharmaceutical Industry | Process for preparing [(s)-(-)alpha-methylamino phenylacetone]2 (2r, 3r)-tartaric acid derivates |
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