IE64605B1 - Method of manufacturing crotonobetaine hydrochloride - Google Patents
Method of manufacturing crotonobetaine hydrochlorideInfo
- Publication number
- IE64605B1 IE64605B1 IE311190A IE311190A IE64605B1 IE 64605 B1 IE64605 B1 IE 64605B1 IE 311190 A IE311190 A IE 311190A IE 311190 A IE311190 A IE 311190A IE 64605 B1 IE64605 B1 IE 64605B1
- Authority
- IE
- Ireland
- Prior art keywords
- hydrochloride
- crotonobetaine
- carnitine
- manufacturing
- mol
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/30—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A novel method for the preparation of crotonobetaine hydrochloride, a starting material for the microbiological preparation of L-carnitine, is described. In this process, carnitine hydrochloride is reacted, in racemic form or in the form of the enantiomers, with acetic anhydride.
Description
METBOD OF MANUFACTURING CROTONOBETAINE HYDROCHLORIDE DESCRIPTION The invention relates to a new method of manufacturing crotonobetaine hydrochloride from carnitine hydrochloride, particularly from racemic carnitine hydrochloride or from D-camitine hydrochloride.
Crotonobetaine hydrochloride is employed inter alia as a starting material in the microbiological synthesis of L-c ami tine, see for example European Patent Application Nos. 0 158 194 and 0 122 794.
A process is described in Chemical Abstracts Vol. 59, 6428 (Binon et al) in which crotonobetaine hydrochloride is produced, with a 78% yield, by reacting DL - caranitine hydrochloride with concentrated sulphuric acid at 13O°C, precipitating the product of this reaction with acetone and treating it with barium chloride. - 2 ί In addition to the problems associated with handling concentrated sulphuric acid, a serious drawback of this v process steins from the barium sulphate, which is produced as a by-product and which cannot be re-circulated.
L-camitine may be obtaining by separating it from the racemate, using a conventional chemical method, such as that described in German Democratic Republic Patent No. 23 217. However, this approach inevitably leads to the production of D-caraitine as a by-product, for which, hitherto, no further use has been found.
It, therefore, is an object of the present invention to provide a process which does not suffer from the aforementioned disadvantages.
According to the present invention, there is provided a method of manufacturing crotonobetaine hydrochloride comprising reacting racemic carnitine hydrochloride, Dcaraitine hydrochloride, or L-camitine hydrochloride, with between 1.5 and 15 mol of acetic anhydride per mol % of carnitine hydrochloride, in the presence of an acid catalyst and at a temperature of between 90 and 130°C. r - 3 Needless to say, the preferred form of carnitine hydrochloride is either the D-form derived from D-camitine produced as a by-product of conventional L-camitine synthesis, or the comparatively inexpensive recemate D L-camitine.
The quantity of acetic anhydride useg is preferably within the range of 1.8 to 2 mol per mol of carnitine hydrochloride.
As regards the acid calayst, preference is given to the use of p-toluene sulphonic acid in a quantity of between 0.5 and 2% by weight in respect of the carnitine hydrochloride employed.
The raction temperature is preferably between 110 and 125°C, the range 115 - 120°C being considered the most advantageous of all.
In this temperature range the reaction is usually completed after about 2 hours. - 4 In a preferred embodiment, after the reaction is substantially complete, a low molecular weight aliphatic alcohol, preferably ethanol, is added to the hot reaction mixture, which is preferably at a temperature of 70 - 80°C, and the resulting mixture is then cooled, to cause the desired crotonobetaine 1 hydrochlorise to be precipitated in a particularly pure state for subsequent isolation.
By employing a method in accordance with the invention, yields over 70% may to be obtained.
The crotonbetaine hydrochloride can be desalted conventionally, for exanple by electro-dialysis, and converted to crotonobetaine.
The product obtained by the inventive method is particularly suitable for use in the microbiological production of L-camitine.
Examples .Og (0.125 mol) of DL-camitine hydrochloride, 0.25g (1.5m mol) of p-toluene sulphonic acid and 25.Og (0.245 mol) of acetic anhydride were heated to 120°C for 2 - 5 10 hours. The resulting dark-coloured solution was allowed to cool down to about 80°C and 20 ml of ethanol were added thereto. During further slow cooling of reaction mixture the product began to precipitate. The resulting suspension was cooled to about 6 °C with an ice water bath, the precipitate was removed by suction and then washed with a small quantity of cold ethanol. The crotonobetaine hydrochloride product was dried in a vacuum.
The product comprised 17.4g of a beige coloured powder with a purity of 96% (HPLC), corresponding to a yield of 73.5%. 1H-NMR, dmso dg: 3.19 (s,-CH3,9H) 4.38 6.33 6.90 13.0 (d 8Hz, -CHj, 2H) (d 15 Hz CH=, 1H) (dt 15 Hz, CH=, 1H) (s wide, -COOH, 1H).
Claims (7)
1. A method of manufacturing crotonobetaine hydrochloride, comprising reacting carnitine hydrochloride, 5 in the form of racemate or a single enantiomer, with 1.5 to 15 mol of acetic anhydride per mol of carnitine hydrochloride, in the presence of an acid catalyst and at a temperature of between 90 and 130°C. 10
2. A method as claimed in claim 1, wherein 1.8 to 2 mol of acetic anhydride is used per mol of carnitine hydrochloride.
3. A method as claimed in either of claims 1 and 2 15 wherein the acid catalyst is p-toluene sulphonic acid and is used in a quantity corresponding to 0.5 to 2% by weight of the carnitine hydrochloride employed.
4. A method as claimed in any of claims 1 to 3, 20 wherein the reaction is carried out in the temperature range of 110 - 125°C.
5. A method as claimed in any of claims 1 to 4, wherein, after the reaction is subtantially complete, a low molecular weight aliphatic alcohol is added to the reaction mixture and the latter is cooled, to isolate the crotonobetaine hydrochloride by precipitation.
6. Crotonbetaine hydrochloride, wherever produced by a method as claimed in any of claims 1 to 5.
7. A method of manufacturing crotonbetaine hydrochloride substantially as hereinbefore described.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH325389 | 1989-09-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE903111A1 IE903111A1 (en) | 1991-03-13 |
| IE64605B1 true IE64605B1 (en) | 1995-08-23 |
Family
ID=4251970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE311190A IE64605B1 (en) | 1989-09-07 | 1990-08-27 | Method of manufacturing crotonobetaine hydrochloride |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0416583B1 (en) |
| JP (1) | JPH03106853A (en) |
| KR (1) | KR910006227A (en) |
| AT (1) | ATE83768T1 (en) |
| CA (1) | CA2023744A1 (en) |
| CZ (1) | CZ278017B6 (en) |
| DD (1) | DD295340A5 (en) |
| DE (1) | DE59000657D1 (en) |
| DK (1) | DK0416583T3 (en) |
| ES (1) | ES2036386T3 (en) |
| FI (1) | FI904363A0 (en) |
| HU (1) | HU205065B (en) |
| IE (1) | IE64605B1 (en) |
| IL (1) | IL95571A (en) |
| NO (1) | NO173731C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4713348B2 (en) * | 2006-01-13 | 2011-06-29 | 日本電産サンキョー株式会社 | Permanent magnet synchronous motor |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1190280B (en) * | 1986-04-24 | 1988-02-16 | Sigma Tau Ind Farmaceuti | PROCEDURE FOR THE PREPARATION OF RANGE-BUTYROBETAIN |
-
1990
- 1990-08-22 CA CA002023744A patent/CA2023744A1/en not_active Abandoned
- 1990-08-27 IE IE311190A patent/IE64605B1/en not_active IP Right Cessation
- 1990-08-31 JP JP2232312A patent/JPH03106853A/en active Pending
- 1990-08-31 KR KR1019900013847A patent/KR910006227A/en not_active Application Discontinuation
- 1990-09-03 IL IL9557190A patent/IL95571A/en not_active IP Right Cessation
- 1990-09-04 FI FI904363A patent/FI904363A0/en not_active IP Right Cessation
- 1990-09-05 ES ES199090117091T patent/ES2036386T3/en not_active Expired - Lifetime
- 1990-09-05 EP EP90117091A patent/EP0416583B1/en not_active Expired - Lifetime
- 1990-09-05 AT AT90117091T patent/ATE83768T1/en not_active IP Right Cessation
- 1990-09-05 DK DK90117091.0T patent/DK0416583T3/en not_active Application Discontinuation
- 1990-09-05 DE DE9090117091T patent/DE59000657D1/en not_active Expired - Fee Related
- 1990-09-06 HU HU905808A patent/HU205065B/en not_active IP Right Cessation
- 1990-09-06 NO NO903888A patent/NO173731C/en unknown
- 1990-09-07 DD DD90343872A patent/DD295340A5/en not_active IP Right Cessation
- 1990-09-07 CZ CS904362A patent/CZ278017B6/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR910006227A (en) | 1991-04-27 |
| HU905808D0 (en) | 1991-03-28 |
| DD295340A5 (en) | 1991-10-31 |
| EP0416583B1 (en) | 1992-12-23 |
| NO173731B (en) | 1993-10-18 |
| ATE83768T1 (en) | 1993-01-15 |
| IE903111A1 (en) | 1991-03-13 |
| IL95571A (en) | 1995-05-26 |
| NO903888D0 (en) | 1990-09-06 |
| CA2023744A1 (en) | 1991-03-08 |
| NO173731C (en) | 1994-01-26 |
| DE59000657D1 (en) | 1993-02-04 |
| DK0416583T3 (en) | 1993-02-01 |
| EP0416583A1 (en) | 1991-03-13 |
| JPH03106853A (en) | 1991-05-07 |
| FI904363A0 (en) | 1990-09-04 |
| HUT54971A (en) | 1991-04-29 |
| IL95571A0 (en) | 1991-06-30 |
| CZ278017B6 (en) | 1993-07-14 |
| ES2036386T3 (en) | 1993-05-16 |
| CZ436290A3 (en) | 1993-01-13 |
| HU205065B (en) | 1992-03-30 |
| NO903888L (en) | 1991-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2017719C1 (en) | Method of quadratic acid synthesis | |
| EP1024137B1 (en) | Resolution of amines | |
| RU1797607C (en) | Process for preparing [@]-@@@-ethyl-2-oxo-1-pyrrolidine acetamide | |
| CA1310017C (en) | Process for the preparation of 2, 6-dichlorodiphenylamino-acetic acid derivatives | |
| CA1299584C (en) | Process for producing 1,6-di(n -cyano-n -guanidino) hexane | |
| IE64605B1 (en) | Method of manufacturing crotonobetaine hydrochloride | |
| US2543345A (en) | Method of preparing glutamic acid amides | |
| US6803467B2 (en) | Intermediates for the production of quinolone carboxylic acid derivatives | |
| US2877220A (en) | Method of preparing lysine | |
| JPH02306947A (en) | Preparation of chiral bata-amino acid | |
| EP0359438B1 (en) | Pyridazinone manufacture | |
| KR0131338B1 (en) | 1,4, dihydro-pyridine intermediates | |
| EP0052094A1 (en) | N-isopropoxycarbonylphenylglycines and their production | |
| CA2305580A1 (en) | Process for production of substituted alkylamine or its salt | |
| US3060192A (en) | Production of enantiomers of alphamethyl-phenethyl hydrazine and intermediate | |
| KR0163042B1 (en) | Process for the preparation of 4-amino-5-hexenic acids | |
| EP0343597B1 (en) | Preparation of tris (2-cyanoethyl) amine | |
| CN111285854A (en) | Preparation method of fludioxonil | |
| US6002015A (en) | Method of producing 1,2,4-triazole | |
| EP0320898A2 (en) | Processes and compounds useful for resolving 1-methyl-3-phenylpropylamine | |
| SU1293171A1 (en) | Method of producing n-acetyl-d,l-alanine | |
| SU1648943A1 (en) | Method for producing difluoro-maleic acid | |
| US5260431A (en) | Nitroanilinesulfonic acids and the preparation of phenylenediaminesulfonic acids | |
| JPH0413653A (en) | Production of alpha-amino-beta-hydroxyvaleric acid | |
| RU1626647C (en) | Method of d-(+)-biotin preparing |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |