CN1865231A - Propionyl-L-carnitine inner salt synthesis method - Google Patents
Propionyl-L-carnitine inner salt synthesis method Download PDFInfo
- Publication number
- CN1865231A CN1865231A CN 200610092049 CN200610092049A CN1865231A CN 1865231 A CN1865231 A CN 1865231A CN 200610092049 CN200610092049 CN 200610092049 CN 200610092049 A CN200610092049 A CN 200610092049A CN 1865231 A CN1865231 A CN 1865231A
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- CN
- China
- Prior art keywords
- propionyl
- carnitine
- add
- weight parts
- acetone
- 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.)
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- UFAHZIUFPNSHSL-MRVPVSSYSA-N O-propanoyl-L-carnitine Chemical compound CCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C UFAHZIUFPNSHSL-MRVPVSSYSA-N 0.000 title claims abstract description 20
- 238000001308 synthesis method Methods 0.000 title 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 40
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000001914 filtration Methods 0.000 claims abstract description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 15
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims abstract description 13
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims abstract description 12
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims abstract description 11
- 235000019260 propionic acid Nutrition 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 238000001556 precipitation Methods 0.000 claims description 12
- 238000010189 synthetic method Methods 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 11
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 238000009413 insulation Methods 0.000 claims description 7
- KTFMPDDJYRFWQE-DDWIOCJRSA-N (3r)-3-propanoyloxy-4-(trimethylazaniumyl)butanoate;hydrochloride Chemical compound [Cl-].CCC(=O)O[C@H](CC(O)=O)C[N+](C)(C)C KTFMPDDJYRFWQE-DDWIOCJRSA-N 0.000 claims description 6
- JXXCENBLGFBQJM-UHFFFAOYSA-N (3-carboxy-2-hydroxypropyl)-trimethylazanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC(O)CC(O)=O JXXCENBLGFBQJM-UHFFFAOYSA-N 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000000247 postprecipitation Methods 0.000 claims description 2
- 238000005057 refrigeration Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 3
- 238000013019 agitation Methods 0.000 abstract 2
- 241000143437 Aciculosporium take Species 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- 239000012467 final product Substances 0.000 abstract 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 abstract 1
- 238000004321 preservation Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 5
- 238000010792 warming Methods 0.000 description 5
- -1 propionyl-L-carnitine hydrochlorides Chemical class 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 3
- JXXCENBLGFBQJM-FYZOBXCZSA-N [(2r)-3-carboxy-2-hydroxypropyl]-trimethylazanium;chloride Chemical class [Cl-].C[N+](C)(C)C[C@H](O)CC(O)=O JXXCENBLGFBQJM-FYZOBXCZSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
This invention provides a method for synthesizing propionyl-L-carnitine inner salt, comprising: a. take L-Carnitine or L-Carnitine hydrochlorate, add in p-toluenesulfonic acid, dissolve with propanoic acid with agitation; b. slowly add in propionyl chloride, after heating-up and heat preservation, cool down to the temperature, then add in acetone, after agitation and filtration, add in ethyl ether, agitate and send the white precipitant liquor to cold storage, after filtration and drying, obtain the propionyl-L-L-Carnitine hydrochlorate; c. dissolve propionyl-L-L-Carnitine hydrochlorate in ethanol, vent in ammonia gas, after removing precipitant by filtration, add in acetone and ethyl ether, and obtain the final product propionyl-L-L-Carnitine hydrochlorate by filtration.
Description
Technical field
The present invention relates to the method for propionyl-L-carnitine inner salt.
Background technology
The synthetic method that English Patent 2048268A announces is that the L-Carnitine is dissolved in trifluoroacetic acid, drip propionyl chloride, 40～50 degrees centigrade of reactions are filtered, wherein make solvent with trifluoroacetic acid, the cost height pollutes heavy, workman's operational danger is big, and adopt other solvents to exist to be difficult to dissolving, problem such as by product is many, thus solvent to select be the key and the difficult point of restriction synthesis technique.
Summary of the invention
It is low to the purpose of this invention is to provide a kind of raw materials cost, pollutes for a short time, and workman's operational danger is little and be easy to dissolve and the synthetic method of the few propionyl-L-carnitine inner salt of by product.
Purpose of the present invention can realize by following technical measures:
This synthetic method is that a. gets L-Carnitine or L-Carnitine hydrochloride earlier, adds tosic acid, is that solvent is in stirring dissolving down again with the propionic acid; B. slowly adds propionyl chloride then, through heating up, take out after the insulation reaction and being cooled to room temperature, add acetone again, through stirring and filter back adding ether, and then will send refrigeration through stir producing adularescent precipitation lye, at last after filtration, dry propionyl-L-carnitine hydrochloride; C. the propionyl-L-carnitine hydrochloride is dissolved in ethanol, feeds ammonia again, treat that the filtering post precipitation adds acetone, ether again, get propionyl-L-carnitine inner salt at last after filtration.
Purpose of the present invention also can realize by following technical measures:
The described tosic acid of a operation: L-Carnitine or L-Carnitine hydrochloride=1～6: 15～19 weight parts;
The add-on of the described propionyl chloride of b operation is 3～30 weight parts, and described holding temperature is 45～50 ℃, and the add-on of described acetone is 380～420 weight parts, and the add-on of described ether is 480～520 weight parts;
The add-on of the described acetone of c operation is 380～420 weight parts, and the add-on of described ether is 480～520 weight parts.
Further say, the synthetic method of propionyl-L-carnitine inner salt of the present invention, adopting the acylation reaction of L-Carnitine and propionyl chloride is solvent with the propionic acid, carries out under the Catalyzed by p-Toluenesulfonic Acid condition.Get the L-Carnitine or the L-Carnitine hydrochloride of 15～19 weight parts earlier, the tosic acid that adds 1～6 weight part, add propionic acid again and make solvent, it is dissolved fully, the back slowly adds the propionyl chloride of 3～30 weight parts, be warming up to 45～50 degrees centigrade again, take out and be cooled to room temperature again after the reaction end down in insulation, the acetone that adds 380～420 weight parts, through stirring and filtering, the back adds the ether of 480～520 weight parts in filtrate, is stirred to the adularescent precipitation and separates out, insert in the refrigerating plant and refrigerate, at last after filtration, the dry propionyl-L-carnitine hydrochloride that gets.Again the propionyl-L-carnitine hydrochloride is dissolved in ethanol, about one hour of logical ammonia, the filtering precipitation adds the acetone of 380～420 weight parts, the ether of 480～520 weight parts, filters, and gets propionyl-L-carnitine inner salt.
The synthetic method of propionyl-L-carnitine inner salt of the present invention is solvent with the propionic acid, and raw materials cost is lower than trifluoroacetic acid greatly, and operational safety, do not have substantially pollution-free, be easy to the dissolving, by product is few.
Embodiment
Embodiment 1:
The synthetic method of propionyl-L-carnitine inner salt of the present invention is as follows: get 16.2 kilograms of L-Carnitines, add 3 kilograms of tosic acid, with 40 kilograms of dry propionic acid, stirring and dissolving, drip 30 kilograms of propionyl chlorides, drip to finish and be warming up to 45 degrees centigrade, insulation reaction 20 hours, room temperature is taken out and be cooled to reaction after finishing, add 410 kilograms in acetone, stirred 2 hours, filter, add 490 kilograms of ether in the filtrate, be stirred to the adularescent precipitation and separate out, put into refrigerator cold-storage, filter, dry 22.5 kilograms of propionyl-L-carnitine hydrochlorides, the yield 88.2% of getting.It is dissolved in ethanol, fed ammonia 1 hour, the filtering precipitation adds 380 kilograms of acetone, 490 kilograms of ether, filters, and gets 18.3 kilograms of propionyl-L-carnitine inner salts, yield 95%.
Embodiment 2:
The synthetic method of propionyl-L-carnitine inner salt of the present invention is as follows: get 18 kilograms of L-Carnitine hydrochlorides, add 6 kilograms of tosic acid, with 60 kilograms of dry propionic acid, stirring and dissolving, drip 5 kilograms of propionyl chlorides, drip to finish and be warming up to 50 degrees centigrade, insulation reaction 20 hours, room temperature is taken out and be cooled to reaction after finishing, add 390 kilograms in acetone, stirred 2 hours, filter, add 510 kilograms of ether in the filtrate, be stirred to the adularescent precipitation and separate out, put into refrigerator cold-storage, filter, dry 24.8 kilograms of propionyl-L-carnitine hydrochlorides, the yield 88.3% of getting.It is dissolved in ethanol, fed ammonia 1 hour, the filtering precipitation adds 400 kilograms of acetone, 500 kilograms of ether, filters, and gets 20.1 kilograms of propionyl-L-carnitine inner salts, yield 94.9%.
Embodiment 3:
The synthetic method of propionyl-L-carnitine inner salt of the present invention is as follows: get 16 kilograms of L-Carnitines, add 2 kilograms of tosic acid, with 40 kilograms of propionic acid, stirring and dissolving, drip 30 kilograms of propionyl chlorides, drip to finish and be warming up to 45 degrees centigrade, insulation reaction 20 hours, room temperature is taken out and be cooled to reaction after finishing, add 410 kilograms in acetone, stirred 2 hours, filter, add 490 kilograms of ether in the filtrate, be stirred to the adularescent precipitation and separate out, put into refrigerator cold-storage, filter, dry 22.1 kilograms of propionyl-L-carnitine hydrochlorides, the yield 88.0% of getting.It is dissolved in ethanol, fed ammonia 1 hour, the filtering precipitation adds 380 kilograms of acetone, 520 kilograms of ether, filters, and gets 18.3 kilograms of propionyl-L-carnitine inner salts, yield 95%.
Embodiment 4:
The synthetic method of propionyl-L-carnitine inner salt of the present invention is as follows: get 18 kilograms of L-Carnitine hydrochlorides, add 5 kilograms of tosic acid, with 60 kilograms of propionic acid, stirring and dissolving, drip 5 kilograms of propionyl chlorides, drip to finish and be warming up to 50 degrees centigrade, insulation reaction 20 hours, room temperature is taken out and be cooled to reaction after finishing, add 380 kilograms in acetone, stirred 2 hours, filter, add 510 kilograms of ether in the filtrate, be stirred to the adularescent precipitation and separate out, put into refrigerator cold-storage, filter, dry 24.8 kilograms of propionyl-L-carnitine hydrochlorides, the yield 88.3% of getting.It is dissolved in ethanol, fed ammonia 1 hour, the filtering precipitation adds 420 kilograms of acetone, 480 kilograms of ether, filters, and gets 20.1 kilograms of propionyl-L-carnitine inner salts, yield 94.9%.
Claims (2)
1, the synthetic method of propionyl-L-carnitine inner salt is characterized in that
A. getting L-Carnitine or L-Carnitine hydrochloride earlier, add tosic acid, is that solvent is in stirring dissolving down again with the propionic acid; Then
B. slowly add propionyl chloride, through heating up, take out after the insulation reaction and being cooled to room temperature, add acetone again, through stirring and filter back adding ether, and then will send refrigeration through stir producing adularescent precipitation lye, at last after filtration, dry propionyl-L-carnitine hydrochloride;
C. the propionyl-L-carnitine hydrochloride is dissolved in ethanol, feeds ammonia again, treat that the filtering post precipitation adds acetone, ether again, get propionyl-L-carnitine inner salt at last after filtration.
2, the synthetic method of propionyl-L-carnitine inner salt according to claim 1 is characterized in that
The described tosic acid of a operation: L-Carnitine or L-Carnitine hydrochloride=1～6: 15～19 weight parts;
The add-on of the described propionyl chloride of b operation is 3～30 weight parts, and described holding temperature is 45～50 ℃, and the add-on of described acetone is 380～420 weight parts, and the add-on of described ether is 480～520 weight parts;
The add-on of the described acetone of c operation is 380～420 weight parts, and the add-on of described ether is 480～520 weight parts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200610092049XA CN100425590C (en) | 2004-10-15 | 2004-10-15 | Propionyl-L-carnitine inner salt synthesis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200610092049XA CN100425590C (en) | 2004-10-15 | 2004-10-15 | Propionyl-L-carnitine inner salt synthesis method |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410035942 Division CN1290821C (en) | 2004-10-15 | 2004-10-15 | Propionyl-L-carnitine synthesis technology and detection method of related substance and its content |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1865231A true CN1865231A (en) | 2006-11-22 |
| CN100425590C CN100425590C (en) | 2008-10-15 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB200610092049XA Expired - Fee Related CN100425590C (en) | 2004-10-15 | 2004-10-15 | Propionyl-L-carnitine inner salt synthesis method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1995010B (en) * | 2006-12-29 | 2012-12-12 | 辽宁科硕营养科技有限公司 | Method for synthesizing propionyl levo-carnitine hydrochlorate |
-
2004
- 2004-10-15 CN CNB200610092049XA patent/CN100425590C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1995010B (en) * | 2006-12-29 | 2012-12-12 | 辽宁科硕营养科技有限公司 | Method for synthesizing propionyl levo-carnitine hydrochlorate |
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| Publication number | Publication date |
|---|---|
| CN100425590C (en) | 2008-10-15 |
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Owner name: SUZHOU LANXITE BIOTECHNOLOGY CO., LTD. Free format text: FORMER OWNER: QIDU PHARMACEUTICAL CO., LTD., SHANDONG PROV. Effective date: 20150428 |
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Free format text: CORRECT: ADDRESS; FROM: 255400 ZIBO, SHANDONG PROVINCE TO: 215123 SUZHOU, JIANGSU PROVINCE |
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Effective date of registration: 20150428 Address after: 215123, Suzhou Jiangsu Industrial Park, if the water 388 nanotechnology, National University Science Park, D building, 7 floor Patentee after: Suzhou Lanxite Biotechnology Co., Ltd. Address before: 255400 Linzi, Shandong province people's road, No. 28 East Road, No. Patentee before: Qidu Pharmaceutical Co., Ltd., Shandong Prov. |
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Address after: 215123 Suzhou Industrial Park, Suzhou, Jiangsu, No. 388, Nanshui, 7 D, National Science and Technology Park, Nanshui University. Patentee after: Suzhou Netac biotechnology Limited by Share Ltd Address before: 215123 Jiangsu Suzhou Industrial Park 388, Nanshui, Nanshui, 7 D, National Science and technology park. Patentee before: Suzhou Lanxite Biotechnology Co., Ltd. |
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| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20081015 Termination date: 20181015 |
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| CF01 | Termination of patent right due to non-payment of annual fee |