CN101125821A - Method for preparing hemostatic 6-amino caproic acid - Google Patents
Method for preparing hemostatic 6-amino caproic acid Download PDFInfo
- Publication number
- CN101125821A CN101125821A CNA2007100597826A CN200710059782A CN101125821A CN 101125821 A CN101125821 A CN 101125821A CN A2007100597826 A CNA2007100597826 A CN A2007100597826A CN 200710059782 A CN200710059782 A CN 200710059782A CN 101125821 A CN101125821 A CN 101125821A
- Authority
- CN
- China
- Prior art keywords
- aminocaprolc acid
- preparation
- exchange resin
- aminocaprolc
- anion exchange
- 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.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 6-aminocaproic acid which is a hemostatic. The preparation method is characterized in that caprolactam is dissolved in diluted hydrochloric acid, heated and refluxed to produce 6-aminocaproic acid hydrochloride which is neutralized by spherical macro-porous styrene type weak alkaline anion exchange resin, thereby acquiring the product after treatment. Compared with other preparation methods, the reaction condition of the method is mild, and metal ion can not be mixed easily, the method is more scientific and rational, the standard of the burn residue required by the original material quality can be realized more easily, white crystal can be obtained from the product without activated carbon decolorizing, the operation is simple, the synthesizing cost is reduced and mass production of the technology is more suitable.
Description
[technical field]
The present invention relates to technical field of organic synthesis, particularly a kind of preparation method of hemostatic drug 6-aminocaprolc acid.
[background technology]
6-aminocaprolc acid (6-Aminohexanoic acid), molecular formula: C
6H
13NO
2It is present domestic and international widely used hemostatic agent, it has tangible curative effect to increase certain severe haemorrhage that causes because of fibrinolytic activity, and oozing of blood or local hemorrhage when being applicable to various surgical operation also are used for noise made in coughing or vomiting blood, digestive tract hemorrhage and Obstetric and Gynecologic Department hemorrhagic illness etc.In prior art, following patent and document relate to the preparation method of 6-aminocaprolc acid, as U.S.Pat2 453,234; Org.syn.Coll.vol II, 28 (1943); Org.syn.Coll.Vol IV, 39 (1963); The Hebei chemical industry, 2003,4,24; Organic synthesis topical reference book (Fan Nengting chief editor), P394 etc.Above-mentioned patented technology and literature method have dependency, and its synthetic route mainly contains following two kinds of methods:
Method one, be raw material, make the 6-aminocaprolc acid hydrochloride through hydrochloric acid hydrolysis, with its dilution, by storng-acid cation exchange resin absorption, standing over night with the hexanolactam; Bleed off behind the liquid again with the water wash resin, to the elutant till the no chlorion; Pass through Zeo-karb, standing over night with weak ammonia; Use the water wash resin, collect elutriant; The elutriant concentrating under reduced pressure is closely dried, adds dehydrated alcohol, separates out crystal under the vigorous stirring, gets the 6-aminocaprolc acid crude product; Crude product is water-soluble, add activated carbon decolorizing, to filter, filtrate concentrates near doing, and adds dehydrated alcohol while hot, separates out crystal, and suction filtration is dry and get.
Method two, be raw material, make the 6-aminocaprolc acid hydrochloride through hydrochloric acid hydrolysis with the hexanolactam, evaporated under reduced pressure in the steam bath, 6-aminocaprolc acid hydrochloride solid; The 6-aminocaprolc acid hydrochloride is water-soluble, handles with yellow lead powder, the aluminium hydroxide that newly makes and oxidation silver powder successively; Again with hydrogen sulfide treatment to remove halogen and metal ion; Solution concentration adds dehydrated alcohol, separates out crystal, and suction filtration is dry and get.
The weak point of above-mentioned synthetic method is:
The 6-aminocaprolc acid hydrochloride aqueous solution that will contain hydrochloric acid in the method one needs standing over night, length consuming time directly by storng-acid cation exchange resin; Without concentrating, because of it contains a large amount of hydrochloric acid, again with the ammoniacal liquor wash-out, and standing over night, ammonia volume is big, length consuming time, complex operation; Nearly one hour of activated carbon decolorizing, length consuming time, loss is big, has increased schedule of operation, has improved synthetic cost.Do not adopt resin absorption in the method two, but the adding of yellow lead powder, aluminium hydroxide, silver suboxide has obviously increased cost; The virose hydrogen sulfide removal metal ion of apparatus, complex procedures is dangerous big.
[summary of the invention]
The present invention is intended to for overcoming the deficiencies in the prior art, and a kind of preparation method of new 6-aminocaprolc acid is provided, and this method reaction conditions gentleness is easy and simple to handle.Reduce preparation cost, improved benefit thus, be suitable for large-scale production.
The present invention addresses the above problem the preparation method that the scheme that is adopted is a kind of hemostatic drug 6-aminocaprolc acid of design.It is characterized in that hexanolactam heating hydrolysis in aqueous hydrochloric acid is made the 6-aminocaprolc acid hydrochloride, again by spherical macroreticular weakly base styrene series anion exchange resin neutralization, the refining 6-aminocaprolc acid that obtains.
The invention has the beneficial effects as follows: the present invention compares with other preparation method, and the reaction conditions gentleness is difficult for the tramp m. ion, and its method is science, reasonable more, and the desired residue on ignition of easier realization bulk drug quality standard is up to standard.Product can obtain white crystal without activated carbon decolorizing, and is easy and simple to handle, reduced synthetic cost, makes its technology be more suitable for large-scale production.
[embodiment]
Preparation process of the present invention is: hexanolactam is dissolved in 10% aqueous hydrochloric acid, reflux, be evaporated to dried so that make in the solution not residual chloride hydrogen, the 6-aminocaprolc acid hydrochloride.Then spherical macroreticular weakly base styrene series anion exchange resin is spent the night with distilled water immersion, the separator column of packing into is with 0.8% ammonia aqueous solution wash-out resin, wash with water again to neutrality, the 6-aminocaprolc acid hydrochloride is water-soluble, in the post of packing into, with water elution, collect elutriant, be evaporated to driedly, add dehydrated alcohol, separate out crystal, filter, drying makes 6-aminocaprolc acid.
Among the present invention, weak base anion-exchange resin is spherical macroreticular weakly base styrene series anion exchange resin, and its model is D370 or D301.
During preparation 6-aminocaprolc acid hydrochloride, every 17g mole number is 0.15 hexanolactam, needs with 10% aqueous hydrochloric acid 65-75ml; The 6-aminocaprolc acid hydrochloride that every 17g hexanolactam makes needs the spherical macroreticular weakly base styrene series anion exchange resin neutralization with 95g; Need to carry out wash-out with 0.8% ammonia aqueous solution 750-800ml.The method of judging the neutralization reaction terminal point is that elutriant is identical with the pH value of distilled water.
The embodiment of the invention:
In the 250mL round-bottomed flask, add 10% aqueous hydrochloric acid of 65ml, 17g (0.15mol) hexanolactam.Stir down reactant boiled 1 hour, be evaporated to dried, the 6-aminocaprolc acid hydrochloride, it is stand-by to be dissolved in 120ml distilled water.
Take by weighing the 95g weak base anion-exchange resin, the adding distil water soaked overnight is filled to (the high 300mm of post in the ion exchange column with it, interior column radius 30mm), 0.8% ammonia aqueous solution with 750ml carries out wash-out, is washed till neutrality with distilled water again, in 6-aminocaprolc acid hydrochloride aqueous solution impouring ion exchange column, with the distilled water wash-out, when treating that the pH value of elutriant and distilled water is identical, stop to collect, be evaporated to dried, add the 120ml dehydrated alcohol, separate out crystal, suction filtration, ethanol is washed, ether is washed, drying gets 6-aminocaprolc acid 16.3g, yield 82.7%, 205～207 ℃ of fusing points, content 98.6% (perchloric acid nonaqueous titrations).
Its synthetic route is:
Claims (8)
1. the preparation method of a hemostatic drug 6-aminocaprolc acid, it is characterized in that hexanolactam heating hydrolysis in aqueous hydrochloric acid is made the 6-aminocaprolc acid hydrochloride, again by spherical macroreticular weakly base styrene series anion exchange resin neutralization, the refining 6-aminocaprolc acid that obtains.
2. the preparation method of hemostatic drug 6-aminocaprolc acid according to claim 1 is characterized in that described preparation process is as follows:
(1) hexanolactam is dissolved in 10% aqueous hydrochloric acid, reflux, be evaporated to dried, the 6-aminocaprolc acid hydrochloride;
(2) spherical macroreticular weakly base styrene series anion exchange resin spends the night with distilled water immersion, and the separator column of packing into is with 0.8% weak ammonia wash-out resin, wash with water again to neutrality, the 6-aminocaprolc acid hydrochloride is water-soluble, in the post of packing into, with water elution, collect elutriant, be evaporated to driedly, add dehydrated alcohol, separate out crystal, filter, drying makes 6-aminocaprolc acid.
3. the preparation method of hemostatic drug 6-aminocaprolc acid according to claim 1 and 2 is characterized in that described spherical macroreticular weakly base styrene series anion exchange resin is D370 or D301.
4. the preparation method of hemostatic drug 6-aminocaprolc acid according to claim 1 and 2, when it is characterized in that preparing the 6-aminocaprolc acid hydrochloride, every 17g mole number is 0.15 hexanolactam, uses 10% aqueous hydrochloric acid 65-75ml.
5. the preparation method of hemostatic drug 6-aminocaprolc acid according to claim 1 and 2 is characterized in that the 6-aminocaprolc acid hydrochloride that every 17g hexanolactam makes, with the spherical macroreticular weakly base styrene series anion exchange resin neutralization of 95g.
6. the preparation method of hemostatic drug 6-aminocaprolc acid according to claim 1 and 2 is characterized in that the spherical macroreticular weakly base styrene series anion exchange resin of every 95g, needs carry out wash-out with 0.8% ammonia aqueous solution 750-800ml.
7. the preparation method of hemostatic drug 6-aminocaprolc acid according to claim 1 and 2 is that elutriant is identical with the pH value of distilled water with the method for terminal point in it is characterized in that judging.
8. according to the preparation method of hemostatic drug 6-aminocaprolc acid of the described arbitrary or combination of claim 3-7, be that elutriant is identical with the pH value of distilled water with the method for terminal point in it is characterized in that judging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100597826A CN101125821A (en) | 2007-09-26 | 2007-09-26 | Method for preparing hemostatic 6-amino caproic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100597826A CN101125821A (en) | 2007-09-26 | 2007-09-26 | Method for preparing hemostatic 6-amino caproic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101125821A true CN101125821A (en) | 2008-02-20 |
Family
ID=39093974
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007100597826A Pending CN101125821A (en) | 2007-09-26 | 2007-09-26 | Method for preparing hemostatic 6-amino caproic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101125821A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110256268A (en) * | 2019-07-02 | 2019-09-20 | 扬州中宝药业股份有限公司 | A kind of preparation method of aminocaproic acid |
| CN111100025A (en) * | 2019-12-26 | 2020-05-05 | 江苏永安制药有限公司 | Method for preparing aminocaproic acid |
| CN113727685A (en) * | 2019-02-13 | 2021-11-30 | 生物生命有限责任公司 | Wound sealing powder comprising cation exchange resin |
-
2007
- 2007-09-26 CN CNA2007100597826A patent/CN101125821A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113727685A (en) * | 2019-02-13 | 2021-11-30 | 生物生命有限责任公司 | Wound sealing powder comprising cation exchange resin |
| CN110256268A (en) * | 2019-07-02 | 2019-09-20 | 扬州中宝药业股份有限公司 | A kind of preparation method of aminocaproic acid |
| CN111100025A (en) * | 2019-12-26 | 2020-05-05 | 江苏永安制药有限公司 | Method for preparing aminocaproic acid |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101486669B (en) | Method for synthesizing taurine | |
| CN1843938A (en) | Method for preparing vanadium pentoxide | |
| CN101830818B (en) | Method for preparing anhydrous betaine | |
| CN103613501A (en) | Method for preparing tributyl citrate by taking macroporous strong-acid cation exchange resin as catalyst | |
| Zhao et al. | N-methyl-2-pyrrolidonium-based Brönsted-Lewis acidic ionic liquids as catalysts for the hydrolysis of cellulose | |
| CN101125821A (en) | Method for preparing hemostatic 6-amino caproic acid | |
| CN107118115B (en) | Preparation method of ferrous glycinate chelate | |
| CN101857550B (en) | Method for producing 6-aminocaproic acid hydrochloride and 6-aminocaproic acid by using nylon-6 waste through depolymerization | |
| CN104327129A (en) | Method for preparing glucosamine hydrochloride by taking crab shells as raw materials | |
| CN102240502B (en) | Preparation method of amino immobilized ionic liquid | |
| CN113621834A (en) | Method for selectively dephosphorizing molybdenum and phosphorus mixed solution | |
| CN108033903A (en) | Synthesis process for D L-p-methylsulfonylphenylserine ethyl ester with water esterification | |
| CN101100435A (en) | Method for preparing L-ornithine-L-aspartate | |
| CN101973870B (en) | Preparation of glycollic acid from oxalaldehyde by intramolecular disproportionation method | |
| CN102502570B (en) | Production method of medical sodium metavanadate | |
| CN109251153A (en) | A kind of synthetic method of cinnamonitrile | |
| CN111253272B (en) | Method for preparing benzamide compound | |
| CN102344378B (en) | Amino alcohol preparation method using aqueous amino acid | |
| CN102702276B (en) | Postprocessing method for glycal reaction solution | |
| CN102500397B (en) | Preparation method for solid super acid catalyst for synthesis of levulinic acid and application of solid super acid catalyst | |
| RU2129540C1 (en) | Succinic acid or its salts production method | |
| CN101759605A (en) | Preparation method of amino-substituted hydrocarbyl sulfonic acid | |
| CN109970569A (en) | A kind of preparation method of N, N- dimethyl-p-phenylenediamine's hydrochloride | |
| CN101492234B (en) | Production process for urban sewage water, sewage sludge dehydrating agent and method of use thereof | |
| CN110184308A (en) | A kind of preparation method of (R)-o-chloromandelic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |