CN1616420A - Process for producing ethyl creatine ester hydrochloride - Google Patents
Process for producing ethyl creatine ester hydrochloride Download PDFInfo
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- CN1616420A CN1616420A CN 200410064672 CN200410064672A CN1616420A CN 1616420 A CN1616420 A CN 1616420A CN 200410064672 CN200410064672 CN 200410064672 CN 200410064672 A CN200410064672 A CN 200410064672A CN 1616420 A CN1616420 A CN 1616420A
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- ester hydrochloride
- creatine ester
- ethyl
- ethyl creatine
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Abstract
The production process of ethyl creatine ester hydrochloride includes the following steps: preparing mixed solution with ethanol of concentration over 99 % and hydrogen chloride of content of 8-10 wt%; throwing dried creatine into the medicine solution via stirring to produce ethyl creatine ester hydrochloride, with the weight ratio between ethanol and creatine being 7.5-8.5; and separating synthetic ethyl creatine ester hydrochloride from the solution to obtain ethyl creatine ester hydrochloride. The present invention has the features of high product purity, easy drying, etc. and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of manufacturing process of ethyl creatine ester hydrochloride.
Background technology
In known document, A.W.Dox and the L.Yoder research report delivered as the journal of biological chemistry (J.Biol.Chem.1922.54.671.) of the U.S., what JACS (J.A.C.S.1955.77.178.) was published closes the research report of writing by people such as J.O.MOLD and R.C.GORE, and the clear 32-9076 of Japan's special permission, the preparation of the ethyl creatine ester hydrochloride that 32-9078 explained, all be that the creatine that drying is crossed is placed dehydrated alcohol, feed hydrogenchloride at normal temperatures to saturated, stirred for several hour is separated out crystallization, then it is carried out suction filtration, inhale de-chlorine hydride gas, promptly obtain ethyl creatine ester hydrochloride.But in ethanol, feed hydrogenchloride to saturated, make the consumption of hydrogenchloride surpass 8～10 times of actual amount, not only easily cause environmental pollution and loss of material, and the existence of a large amount of hydrogenchloride can absorb more water, make product be difficult to drying, also increase the chance that generates the creatinine hydrochloride, reduced the purity of product.
Summary of the invention
The object of the invention provides the manufacturing process that a kind of hydrogenchloride uses economic ethyl creatine ester hydrochloride.
Technical scheme of the present invention is: a kind of manufacturing process of ethyl creatine ester hydrochloride, and it may further comprise the steps: (1), be that ethanol and hydrogenchloride more than 99% is mixed and made into solution with concentration, wherein, the weight ratio content of hydrogenchloride is 8%～10%; (2), in mixing solutions, drop into the dry creatine of crossing, stir the back and generate ethyl creatine ester hydrochloride, wherein the weight proportion of ethanol and creatine is 7.5: 1～8.5: 1; (3), the synthetic ethyl creatine ester hydrochloride is separated from ethanol and hydrogen chloride solution, obtain ethyl creatine ester hydrochloride.
The present invention compared with prior art, has following advantage: the mixing solutions of at first making ethanol and hydrogenchloride according to weight proportion, and then drop into quantitative creatine by standard and in mixing solutions, react, again the ethyl creatine ester hydrochloride of building-up reactions gained is separated at last, because ethanol, the weight of hydrogenchloride and creatine is by the reaction needed proportioning, so can avoid feeding in the mixing solutions excess chlorination hydrogen, both reduced raw-material consumption, make the product after the building-up reactions directly separate dry getting final product again, and the probability that generates impurity such as creatinine hydrochloride in the reaction process is also less, can obtain highly purified product.
Embodiment
Creatine is a kind of inner salt with amino and carboxyl, solubleness in water and alcohol is all very little, synthesize ethyl creatine ester hydrochloride, must earlier creatine be made hydrochloride it is dissolved in the ethanol, synthesize ethyl creatine ester hydrochloride then in the presence of hydrochloric acid, reaction equation is:
The invention provides a kind of manufacturing process that is suitable for the ethyl creatine ester hydrochloride of suitability for industrialized production, it may further comprise the steps: (1), be that ethanol and hydrogenchloride more than 99% is mixed and made into solution with concentration, and wherein, the weight ratio content of hydrogenchloride is 8%～10%; (2), in mixing solutions, drop into the dry creatine of crossing, stir the back and generate ethyl creatine ester hydrochloride, wherein the weight proportion of ethanol and creatine is 7.5: 1～8.5: 1; (3), the synthetic ethyl creatine ester hydrochloride is separated from ethanol and hydrogen chloride solution, obtain ethyl creatine ester hydrochloride.
For improving the precision of raw material ratio, the employed concentration of ethanol of described step (1) is more than 99.7%, and the weight ratio content of the hydrogenchloride in the mixing solutions is 8.7～9.3%, and hydrogenchloride with need before ethanol mixes through vitriol oil drying, the method for dry hydrogen chloride is for using vitriol oil drying.The creatine that drops in the mixing solutions in the described step (2) is dry mistake under 103 ℃～107 ℃ the condition in temperature.And the reaction of the synthetic ethyl creatine ester hydrochloride in the described step (2) is to carry out under temperature is 10 ℃～20 ℃ condition, and the reaction times is 4～8 hours, then the temperature of reaction soln is reduced to 0 ℃, stops to stir, and keeps 3～5 hours again.For improving reaction efficiency and reasonableness, the temperature of reaction of described synthetic ethyl creatine ester hydrochloride is 12 ℃～17 ℃, and the reaction times of described synthetic ethyl creatine ester hydrochloride is 5～7 hours.
Isolate the ethyl creatine ester hydrochloride crystal through suction filtration with after adopting whizzer to deviate from hydrogenchloride and ethanolic soln in the described step (3).And the mode that only adopts suction filtration can't obtain the exsiccant ethyl creatine ester hydrochloride, when suitability for industrialized production, must carry out drying to ethyl creatine ester hydrochloride and just can obtain high-quality product, drying means is: described step (3) is placed on ethyl creatine ester hydrochloride afterwards carries out drying in the moisture eliminator, the exsiccant process is at first respectively with 25 ℃～30 ℃, 50 ℃～60 ℃ dry air dry 1.5～2.5 hours respectively, under 75 ℃～85 ℃ condition of negative pressure dry 1～3 hour then.
Introduce concrete two embodiment below.
Embodiment one: be furnished with agitator at one, thermometer, add 80 gram dehydrated alcohols (concentration is more than 99.7%) in the flask of charging opening and venting port and make mixing solutions with 8 gram hydrogenchloride, the outer ice-water bath attemperation of flask also begins to stir, when being 15 ℃, solution temperature adds 10 grams dry creatine of crossing under 105 ℃ of conditions, mixing solutions begins muddiness and suspended substance is arranged, very fast solution becomes is limpid, keeping temperature of reaction is 15 ℃, and the maintenance reaction times is 4 hours, in the reaction soln in the flask by close grain occurring to stiff, be cooled to 0 ℃ gradually, stop to stir, and left standstill 3 hours, make the temperature of charge in the flask rise to 15 ℃, with material through suction filtration and after deviating from filtrate the wet crystal of gained be placed on and slough residual solution in the whizzer again, crystallization is placed in the moisture eliminator with microwell plate, the slave plate bottom is blown into dry air at twice, the temperature of dry air is respectively 25 ℃ and 55 ℃, each is dry 2 hours, carry out the negative pressure drying 1 hour under 80 ℃ then, obtain ethyl creatine ester hydrochloride product 11 grams, the purity of ethyl creatine ester hydrochloride is 99.3%.
Embodiment two: agitator is being housed, thermometer, charge cavity, in the reactor with chuck of outage (2000 liters), the hydrogenchloride that contains that drops into that 1200 kilograms of dehydrated alcohols (concentration is more than 99.7%) and hydrogen chloride gas make is 9% solution, cool off and begin with chuck and stir, make temperature remain on 15 ℃, add 150 kilograms of the dry anhydrous creatines of crossing, controlled temperature is between 10 ℃～20 ℃, reaction times is continuously 6 hours, feed liquid becomes limpid by muddiness in the still, become muddy immediately gradually, up to the solution becomes stiff, make feed temperature reduce to 0 ℃, stop to stir, left standstill 4 hours, when treating that temperature rises to 15 ℃ by 0 ℃, material is positioned in the suction filter, slough residual solution through whizzer again behind the most of liquid of elimination, the wet crystal of gained is placed in the instrument air dryer, by the dry air of 25 ℃～30 ℃ and 50 ℃～60 ℃ dry 3 hours respectively, under 80 ℃ condition of negative pressure dry 2 hours then, get 175 kilograms of products after the cooling, the content of ethyl creatine ester hydrochloride is 99.2%.
By above two embodiment as seen, technology of the present invention is reasonable, can obtain highly purified product, is applicable to suitability for industrialized production.
Claims (10)
1, a kind of manufacturing process of ethyl creatine ester hydrochloride, it is characterized in that: it may further comprise the steps: (1), be that ethanol and hydrogenchloride more than 99% is mixed and made into solution with concentration, wherein, the weight ratio content of hydrogenchloride is 8%～10%; (2), in mixing solutions, drop into the dry creatine of crossing, stir the back and generate ethyl creatine ester hydrochloride, wherein the weight proportion of ethanol and creatine is 7.5: 1～8.5: 1; (3), the synthetic ethyl creatine ester hydrochloride is separated from ethanol and hydrogen chloride solution, obtain ethyl creatine ester hydrochloride.
2, the manufacturing process of ethyl creatine ester hydrochloride according to claim 1 is characterized in that: the alcohol concn in the described step (1) is more than 99.7%.
3, the manufacturing process of ethyl creatine ester hydrochloride according to claim 1 is characterized in that: the weight ratio content of the hydrogenchloride in the mixing solutions in the described step (1) is 8.7～9.3%.
4, the manufacturing process of ethyl creatine ester hydrochloride according to claim 1 is characterized in that: the creatine that drops in the mixing solutions in the described step (2) is dry mistake under 103 ℃～107 ℃ the condition in temperature.
5, the manufacturing process of ethyl creatine ester hydrochloride according to claim 1, it is characterized in that: the reaction of the synthetic ethyl creatine ester hydrochloride in the described step (2) is to carry out under temperature is 10 ℃～20 ℃ condition, reaction times is 4～8 hours, then the temperature of reaction soln is reduced to 0 ℃, stop to stir, kept again 3～5 hours.
6, the manufacturing process of ethyl creatine ester hydrochloride according to claim 5 is characterized in that: the temperature of reaction of described synthetic ethyl creatine ester hydrochloride is 12 ℃～17 ℃.
7, the manufacturing process of ethyl creatine ester hydrochloride according to claim 5 is characterized in that: the reaction times of described synthetic ethyl creatine ester hydrochloride is 5～7 hours.
8, the manufacturing process of ethyl creatine ester hydrochloride according to claim 1 is characterized in that: isolate the ethyl creatine ester hydrochloride crystal through suction filtration with after adopting whizzer to deviate from hydrogenchloride and ethanolic soln in the described step (3).
9, the manufacturing process of ethyl creatine ester hydrochloride according to claim 1, it is characterized in that: described step (3) is placed on ethyl creatine ester hydrochloride afterwards carries out drying in the moisture eliminator, the exsiccant process is at first respectively with 25 ℃～30 ℃, 50 ℃～60 ℃ dry air dry 1.5～2.5 hours respectively, under 75 ℃～85 ℃ condition of negative pressure dry 1～3 hour then.
10, the manufacturing process of ethyl creatine ester hydrochloride according to claim 1 is characterized in that: the hydrogenchloride in the described step (1) with to carry out drying before ethanol mixes.
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| CN 200410064672 CN1240676C (en) | 2004-09-17 | 2004-09-17 | Process for producing ethyl creatine ester hydrochloride |
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| CN 200410064672 CN1240676C (en) | 2004-09-17 | 2004-09-17 | Process for producing ethyl creatine ester hydrochloride |
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| CN1616420A true CN1616420A (en) | 2005-05-18 |
| CN1240676C CN1240676C (en) | 2006-02-08 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101066938A (en) * | 2007-06-15 | 2007-11-07 | 上海博速医药科技有限公司 | Prepn process of creatine hydrochloride |
| CN103319376A (en) * | 2013-06-21 | 2013-09-25 | 太仓市新毛涤纶化工有限公司 | Preparation method of creatine hydrochloride |
| EP2692719A1 (en) | 2012-07-30 | 2014-02-05 | Commissariat à l'Énergie Atomique et aux Énergies Alternatives | Method for preparing creatine fatty esters, creatine fatty esters thus prepared and uses thereof |
| CN104262203A (en) * | 2014-09-05 | 2015-01-07 | 张家港威胜生物医药有限公司 | Preparation method of creatine ethyl ester hydrochloride |
| CN116143663A (en) * | 2023-01-19 | 2023-05-23 | 安徽泰格生物科技有限公司 | Preparation method of creatine ethyl ester hydrochloride |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100371316C (en) * | 2006-07-19 | 2008-02-27 | 天津天成制药有限公司 | Process for preparing ethyl creatine hydrochloride |
-
2004
- 2004-09-17 CN CN 200410064672 patent/CN1240676C/en active Active
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101066938A (en) * | 2007-06-15 | 2007-11-07 | 上海博速医药科技有限公司 | Prepn process of creatine hydrochloride |
| CN101066938B (en) * | 2007-06-15 | 2013-09-11 | 上海博速医药科技有限公司 | Prepn process of creatine hydrochloride |
| EP2692719A1 (en) | 2012-07-30 | 2014-02-05 | Commissariat à l'Énergie Atomique et aux Énergies Alternatives | Method for preparing creatine fatty esters, creatine fatty esters thus prepared and uses thereof |
| WO2014019855A1 (en) | 2012-07-30 | 2014-02-06 | Commissariat à l'énergie atomique et aux énergies alternatives | Method for preparing creatine fatty esters, creatine fatty esters thus prepared and uses thereof |
| US10144705B2 (en) | 2012-07-30 | 2018-12-04 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Method for preparing creatine fatty esters, creatine fatty esters thus prepared and uses thereof |
| CN103319376A (en) * | 2013-06-21 | 2013-09-25 | 太仓市新毛涤纶化工有限公司 | Preparation method of creatine hydrochloride |
| CN103319376B (en) * | 2013-06-21 | 2015-11-18 | 太仓市新毛涤纶化工有限公司 | The preparation method of creatine hydrochloride |
| CN104262203A (en) * | 2014-09-05 | 2015-01-07 | 张家港威胜生物医药有限公司 | Preparation method of creatine ethyl ester hydrochloride |
| CN116143663A (en) * | 2023-01-19 | 2023-05-23 | 安徽泰格生物科技有限公司 | Preparation method of creatine ethyl ester hydrochloride |
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| CN1240676C (en) | 2006-02-08 |
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Address after: 215000 New Mao Wanfeng Village, Chengxiang Town, Taicang City, Suzhou City, Jiangsu Province Patentee after: TAICANG XINMAO POLYESTER CHEMICAL Co.,Ltd. Address before: 215414 new Mao Town, Taicang, Jiangsu Patentee before: XINMAO DACRON CHEMICAL GENERAL PLANT, TAICANG CITY |
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