SE448724B - PROCEDURE FOR PREPARING CARNITINE CHLORIDE - Google Patents
PROCEDURE FOR PREPARING CARNITINE CHLORIDEInfo
- Publication number
- SE448724B SE448724B SE8204117A SE8204117A SE448724B SE 448724 B SE448724 B SE 448724B SE 8204117 A SE8204117 A SE 8204117A SE 8204117 A SE8204117 A SE 8204117A SE 448724 B SE448724 B SE 448724B
- Authority
- SE
- Sweden
- Prior art keywords
- carnitine
- chloride
- acid chloride
- chlorinating agent
- hours
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- PHIQHXFUZVPYII-UHFFFAOYSA-N carnitine Chemical compound C[N+](C)(C)CC(O)CC([O-])=O PHIQHXFUZVPYII-UHFFFAOYSA-N 0.000 title description 5
- 229960000678 carnitine chloride Drugs 0.000 title 1
- 229960004203 carnitine Drugs 0.000 claims description 20
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 14
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 13
- 239000012320 chlorinating reagent Substances 0.000 claims description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 7
- HKYGSMOFSFOEIP-UHFFFAOYSA-N dichloro(dichloromethoxy)methane Chemical compound ClC(Cl)OC(Cl)Cl HKYGSMOFSFOEIP-UHFFFAOYSA-N 0.000 claims description 5
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 claims 3
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 150000004702 methyl esters Chemical class 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- GUYHPGUANSLONG-SNAWJCMRSA-N (E)-4-(trimethylammonio)but-2-enoate Chemical compound C[N+](C)(C)C\C=C\C([O-])=O GUYHPGUANSLONG-SNAWJCMRSA-N 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- -1 dichloromethyl ester Chemical class 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 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 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- 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
- C07C229/04—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 saturated
- C07C229/22—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 saturated the carbon skeleton being further substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- 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
-
- 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
- C07C227/18—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 involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
- C07C59/115—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
448 724 “~ a 2 Det har nu överraskande befunnits att det är möjligt att överföra D,L-karnitin till syrakloriden av D,L-karnitin med utomordentligt goda utbyten utan bildning av oacceptabla mängder biprodukter ur industriell synpunkt (i synnerhet krotonoyl-betain). Detta åstadkommes genom klorering av D,L- karnitin utan att hydroxylgruppen tidigare blivit skyddad (t.ex. genom hydroxylgruppens överföring till en acetylgrupp enligt teknikens ståndpunkt) under förutsättning att vissa kritiska betingelser uppfylles. It has now surprisingly been found that it is possible to convert D, L-carnitine to the acid chloride of D, L-carnitine in extremely good yields without the formation of unacceptable amounts of by-products from an industrial point of view (in particular crotonoyl betaine). . This is accomplished by chlorination of D, L-carnitine without the hydroxyl group having previously been protected (eg by the transfer of the hydroxyl group to an acetyl group according to the prior art) provided that certain critical conditions are met.
I själva verket har det befunnits att det molära för- hållandet mellan karnitin och kloreringsmedel, reaktions- temperaturen och reaktionstiden är kritiska parametrar, som påverkar överföringen av D,L-karnitin till motsvarande syra- klorid och att värdena för de angivna parametrarna måste ligga mellan väldefinierade gränser.In fact, it has been found that the molar ratio of carnitine to chlorinating agent, the reaction temperature and the reaction time are critical parameters which affect the conversion of D, L-carnitine to the corresponding acid chloride and that the values of the specified parameters must be between well-defined boundaries.
Enligt uppfinningen omfattar förfarandet för överföring av karnitin till syrakloriden av karnitin följande åtgärder: Klorering av karnitin med ett kloreringsmedel (bestående av tionylklorid, diklormetyleter eller oxalylklorid) vid rums- temperatur, under reaktionstider mellan ca. 1,5 och 12 tim Nidvid det molära förhållandet mellan karnitin och klorerings- medel ligger mellan 121 och 1:3. ' Fosforpentaklorid skulle även kunna användas som klore- ringsmedel. Detta kloreringsmedel är emellertid icke lämpligt Inpå grund av de« avsevärt längre reaktionstiderna (1-3 dagar) jämfört med de tidigare angivna.According to the invention, the process for the transfer of carnitine to the acid chloride of carnitine comprises the following measures: Chlorination of carnitine with a chlorinating agent (consisting of thionyl chloride, dichloromethyl ether or oxalyl chloride) at room temperature, during reaction times between approx. 1.5 and 12 hours The molar ratio of carnitine to chlorinating agent is between 121 and 1: 3. Phosphorus pentachloride could also be used as a chlorinating agent. However, this chlorinating agent is not suitable due to the considerably longer reaction times (1-3 days) compared to those previously indicated.
I syfte att erhålla höga utbyten vid överföring av karni- tin till syrakloriden är det väsentligt att den angivna tem- peraturen och reaktionstiderna upprätthålles strikt, eftersom till och med små variationer åstadkommer bildning av bipro- dukter. Om oxalylklorid användes som kloreringsmedel, åstad- I kommer t.ex. en reaktionstid av 15 tim nästan fullständig nedbrytning av karnitin till krotonoylbetain.In order to obtain high yields when transferring carnitine to the acid chloride, it is essential that the specified temperature and reaction times be maintained strictly, since even small variations cause the formation of by-products. If oxalyl chloride is used as the chlorinating agent, e.g. a reaction time of 15 hours almost complete degradation of carnitine to crotonoyl betaine.
Följande icke begränsande exempel 1-3 åskådliggör förfarandet enligt föreliggande uppfinning. är , 3. __ 4.4.8 7.2.4 , Exempel 1 (kloreringsmedel: Tionylklorid) 2,25 ml (0,03 mol) SOCl2 sattes till 1,98 9 (0,01 mol) D,L-karnitin-hydroklorid. Efter 1 tim hade allt löst sig fullständigt och efter 1,5 tim var solubiliseringen avslutad. överskottet av SOCl2 avdestillerades och återstoden beståen- de av karnitinsyraklorid tvättades med vattenfri dietyleter.The following non-limiting examples 1-3 illustrate the process of the present invention. is, 3. __ 4.4.8 7.2.4, Example 1 (chlorinating agent: Thionyl chloride) 2.25 ml (0.03 mol) of SOCl 2 were added to 1.98 9 (0.01 mol) of D, L-carnitine hydrochloride. After 1 hour everything had completely dissolved and after 1.5 hours the solubilization was complete. the excess SOCl 2 was distilled off and the residue consisting of carnitine acid chloride was washed with anhydrous diethyl ether.
För identifieringsändamål överfördes syrakloriden till metyl- ester: Reaktionsblandningen kyldes till OOC och 10 ml vat- tenfri metanol tillsattes droppvis; den erhållna blandningen indrevs under vakuum vid 35-40°C, varvid bildades en gelatin- 'artad råprodukt, som efter torkning under vakuum stelnade, men samtidigt dock förblev mycket hygroskopisk.For identification purposes, the acid chloride was converted to methyl ester: The reaction mixture was cooled to 0 ° C and 10 ml of anhydrous methanol was added dropwise; the resulting mixture was evaporated in vacuo at 35-40 ° C to give a gelatinous crude product which solidified on drying under vacuum but remained very hygroscopic.
Tunnskiktskromatografi kloroform 55/ metanol 35/ H20 5/ NH4OH 5 Kärnmagnetiskt resonans-spektrum D20 lösningsmedel 4,82 (1H, m, -CH-); 3,83 (3H, s, -ocH3); 3,55 (2H, OH d, §>fi-cH2-); CH3 3,30 (sn, S, -ü cn3); 2,73 (za, d, ~cH2co-) CH3 Elementaranalys Beräknad Funnen C 45,39 43,99 K.F. ~4% H 8,57 8,54 N 6,62 6,09 cl 16,75 16,92 448 724 .Thin layer chromatography chloroform 55 / methanol 35 / H 2 O 5 / NH 4 OH 5 Nuclear Magnetic Resonance Spectrum D 2 O solvent 4.82 (1H, m, -CH-); 3.83 (3H, s, -ocH 3); 3.55 (2H, OH d, §> fi- cH2-); CH3 3.30 (sn, S, -ü cn3); 2.73 (za, d, ~ cH2co-) CH3 Elemental Analysis Calculated Found C 45.39 43.99 K.F. ~ 4% H 8.57 8.54 N 6.62 6.09 cl 16.75 16.92 448 724.
Exempel 2 (kloreringsmedel: Diklormetyleter) Åtgärderna enligt föregående ekempel upprepades med undantag av att i stället för tionylklorid diklormetyleter (1,78 ml; 0,02 mol) nu kom till användning. Reaktionsbland- ningen fick stå över natten vid rumstemperatur. Överskottet. av diklormetyleter avdestillerades och återstoden tvättades med vattenfri dietyleter. Återstoden visade sig bestå av w karnitinsyraklorid.Example 2 (chlorinating agent: Dichloromethyl ether) The procedures of the previous example were repeated except that instead of thionyl chloride dichloromethyl ether (1.78 ml; 0.02 mol) was now used. The reaction mixture was allowed to stand overnight at room temperature. The surplus. of dichloromethyl ether was distilled off and the residue was washed with anhydrous diethyl ether. The residue was found to consist of w carnitic acid chloride.
CH3 3 Kärnmagnetisk resonans CD3NC 6 3,33 (9H,s,CHñ;>š-); CH3 3,36-3,60 (4H,m,5>§-cH2-, -en coc1); 2 4,40-4,90 (1H,m, -cg-) OH Efter utbyte med D20 antog de kemiska skiftena samma värden som kärnmagnetisk resonansspektrum för karnitin. Den råa syrakloriden överfördes därefter till metylester, som tidigare beskrivits. Metylestern av karnitin visade kemisk- fysikaliska egenskaper svarande mot den tidigare isolerade produkten.CH3 3 Nuclear Magnetic Resonance CD3NC 6 3.33 (9H, s, CHñ;> š-); CH3 3.36-3.60 (4H, m, 5> §-cH2-, -en coc1); 2.40-4.90 (1H, m, -cg-) OH After exchange with D 2 O, the chemical shifts assumed the same values as the nuclear magnetic resonance spectrum of carnitine. The crude acid chloride was then converted to methyl ester, as previously described. The methyl ester of carnitine showed chemical-physical properties corresponding to the previously isolated product.
EXEMPEL 3 Förfarandet i föregående exempel upprepades utom att; i stället för diklormetylester, nu användes oxalylklorid (2,6 ml; 0,01 mol). Reaktionsblandningen hölls under omröring vid 25°C i 4 tim. överskottet av oxalylklorid avdestillerades. Återstoden tvättades med vattenfri dietylester. För identifi- ering överfördes syrakloriden till metylestern, som tidigare beskrivits.EXAMPLE 3 The procedure of the previous example was repeated except that; instead of dichloromethyl ester, oxalyl chloride (2.6 ml; 0.01 mol) was used. The reaction mixture was kept under stirring at 25 ° C for 4 hours. the excess oxalyl chloride was distilled off. The residue was washed with anhydrous diethyl ester. For identification, the acid chloride was transferred to the methyl ester, as previously described.
Metylestern av karnitin visade kemisk-fysikaliska egenskaper svarande mot den tidigare isolerade produkten.The methyl ester of carnitine showed chemical-physical properties similar to the previously isolated product.
.II/ Följande exempel A och B är avsedda att åskådliggöra att de angivna betingelserna absolut måste upprätthållas, om 1): man vill erhålla syrakloriden av karnitin. - r 448 724 i 5 Exempel A (den lämpliga reaktionstemperaturen upprätt- hålles icke) En blandning av karnitin och tionylklorid (molärt för- hållande 1:1) hölls under omrörning vid SOOC. Prover av reaktionsblandningen uttogs efter 30 min, 1 tim och 1,5 tim från reaktionens början. Proverna kontrollerades med tunn- skiktskromatografi (kloroform 55/ CH30H 35/ H20 5/ NH4OH 5) efter spädning med metanol i syfte att överföra eventuell syraklorid till metylestern. _ Efter 30 min iakttogs närvaron av karnitin och metyl- ester av karnitin (Rf 0,4 respektive 0,8)..II / The following examples A and B are intended to illustrate that the stated conditions must be maintained, if 1): one wants to obtain the acid chloride of carnitine. Example 44 (the appropriate reaction temperature is not maintained) A mixture of carnitine and thionyl chloride (molar ratio 1: 1) was kept under stirring at SOOC. Samples of the reaction mixture were taken after 30 minutes, 1 hour and 1.5 hours from the beginning of the reaction. The samples were checked by thin layer chromatography (chloroform 55 / CH 3 OH 35 / H 2 O 5 / NH 4 OH 5) after dilution with methanol in order to transfer any acid chloride to the methyl ester. After 30 minutes, the presence of carnitine and methyl ester of carnitine (Rf 0.4 and 0.8, respectively) were observed.
Efter 1 tim började'krotonoylbetain, karnitin och karnitinmetylester (Rf 0,2 respektive 0,4 respektive 0,8) att bildas.After 1 hour, crotonoyl betaine, carnitine and carnitine methyl ester (Rf 0.2 and 0.4 and 0.8, respectively, respectively) began to form.
Efter 1,5 tim iakttogs närvaron av krotonoylbetain till- sammans med andra nedbrytningsprodukter, som icke kunde iden- tifieras.After 1.5 hours, the presence of crotonoyl betaine was observed along with other degradable products that could not be identified.
Exempel B (reaktionstiden är icke den lämpliga) Tionylklorid (2,3 ml; 0,03 mol) sattes till karnitin- hydroklorid (1,98 g; 0,01 mol) och den erhållna reaktions- blandninden hölls under omrörning vid rumstemperatur i 24 tim. överskottet av tionylklorid avdestillerades och den råa åter- stoden tvättades med vattenfri dietyleter, varvid sålunda er- hölls en fast produkt med smältpunkten 217-218°C.Example B (reaction time is not appropriate) Thionyl chloride (2.3 ml; 0.03 mol) was added to carnitine hydrochloride (1.98 g; 0.01 mol) and the resulting reaction mixture was kept under stirring at room temperature for 24 hours. tim. the excess thionyl chloride was distilled off and the crude residue was washed with anhydrous diethyl ether to give a solid product, m.p. 217-218 ° C.
Tunnskiktskromatografi kloroform 55/ metanol 35/ H20 5/ NH4OH 5/ R f 0,2 Kärnmagnetisk resonans D20 6 7,2-6,2 (2H, m, -CH=CH-); 4,2 (211, d, àfâ-cuz-n CH3 + 3,2 (sm, s, cH3>N-) CH3 448 724 ' I enlighet med vad tunnskiktskromatografi och kärnmagne- tisk resonans-spektrum visar bildas icke syrakloriden av kar- nitin under dessa reaktionsbetingelser. Tvärtom äger dehydra- tisering rum under bildning av krotonoylbetain CH3 c1-13 fi-Cnz-cx-hca-coofl .Thin layer chromatography chloroform 55 / methanol 35 / H 2 O 5 / NH 4 OH 5 / R f 0.2 Nuclear Magnetic Resonance D 2 O 6 7.2-6.2 (2H, m, -CH = CH-); 4.2 (211, d, àfâ-cuz-n CH3 + 3.2 (sm, s, cH3> N-) CH3 448 724 'In accordance with what thin-layer chromatography and nuclear magnetic resonance spectra show, the acid chloride is not formed by vessels nitrite under these reaction conditions, on the contrary dehydration takes place to form crotonoyl betaine CH3 c1-13 fi- Cnz-cx-hca-coo fl.
CH3 ,-r .ÅJ wCH3, -r .ÅJ w
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT48817/81A IT1171360B (en) | 1981-07-03 | 1981-07-03 | PROCEDURE FOR THE PREPARATION OF CARNITINE ACID CHLORIDE |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| SE8204117D0 SE8204117D0 (en) | 1982-07-02 |
| SE8204117L SE8204117L (en) | 1983-01-04 |
| SE448724B true SE448724B (en) | 1987-03-16 |
Family
ID=11268676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8204117A SE448724B (en) | 1981-07-03 | 1982-07-02 | PROCEDURE FOR PREPARING CARNITINE CHLORIDE |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS5815943A (en) |
| KR (1) | KR860001886B1 (en) |
| AT (1) | AT390057B (en) |
| BE (1) | BE893713A (en) |
| CA (1) | CA1186332A (en) |
| CH (1) | CH648546A5 (en) |
| DE (1) | DE3224666A1 (en) |
| DK (1) | DK154425C (en) |
| ES (1) | ES513658A0 (en) |
| FR (1) | FR2510559B1 (en) |
| GB (1) | GB2101133B (en) |
| GR (1) | GR76546B (en) |
| IE (1) | IE53279B1 (en) |
| IL (1) | IL66251A0 (en) |
| IT (1) | IT1171360B (en) |
| LU (1) | LU84244A1 (en) |
| NL (1) | NL189666C (en) |
| SE (1) | SE448724B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1190358B (en) * | 1985-05-24 | 1988-02-16 | Sclavo Spa | PROCEDURE FOR THE PREPARATION OF L-CARNITINA |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3940439A (en) * | 1973-11-14 | 1976-02-24 | G. D. Searle & Co. | Acid chloride synthesis |
| IT1116037B (en) * | 1979-04-23 | 1986-02-10 | Sigma Tau Ind Farmaceuti | ACIL CARNITINE ESTERS AND AMIDS THEIR PREPARATION PROCEDURES AND THERAPEUTIC USE |
| DE2943433A1 (en) * | 1979-10-26 | 1981-05-07 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING CARBONIC ACID HALOGENIDES |
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1981
- 1981-07-03 IT IT48817/81A patent/IT1171360B/en active
-
1982
- 1982-06-24 CH CH3884/82A patent/CH648546A5/en not_active IP Right Cessation
- 1982-06-25 IE IE1524/82A patent/IE53279B1/en not_active IP Right Cessation
- 1982-06-29 GB GB08218824A patent/GB2101133B/en not_active Expired
- 1982-06-30 LU LU84244A patent/LU84244A1/en unknown
- 1982-06-30 DK DK295482A patent/DK154425C/en not_active IP Right Cessation
- 1982-06-30 CA CA000406463A patent/CA1186332A/en not_active Expired
- 1982-06-30 BE BE0/208502A patent/BE893713A/en not_active IP Right Cessation
- 1982-07-01 GR GR68615A patent/GR76546B/el unknown
- 1982-07-01 DE DE19823224666 patent/DE3224666A1/en active Granted
- 1982-07-01 KR KR8202945A patent/KR860001886B1/en active
- 1982-07-02 AT AT0257382A patent/AT390057B/en not_active IP Right Cessation
- 1982-07-02 ES ES513658A patent/ES513658A0/en active Granted
- 1982-07-02 JP JP57116084A patent/JPS5815943A/en active Granted
- 1982-07-02 SE SE8204117A patent/SE448724B/en not_active IP Right Cessation
- 1982-07-02 FR FR8211685A patent/FR2510559B1/en not_active Expired
- 1982-07-02 NL NLAANVRAGE8202677,A patent/NL189666C/en not_active IP Right Cessation
- 1982-07-07 IL IL66251A patent/IL66251A0/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| KR840000475A (en) | 1984-02-22 |
| DE3224666C2 (en) | 1991-01-24 |
| IE821524L (en) | 1983-01-03 |
| JPH0244300B2 (en) | 1990-10-03 |
| GR76546B (en) | 1984-08-10 |
| BE893713A (en) | 1982-10-18 |
| DK295482A (en) | 1983-01-04 |
| SE8204117D0 (en) | 1982-07-02 |
| DE3224666A1 (en) | 1983-01-20 |
| IT1171360B (en) | 1987-06-10 |
| NL189666C (en) | 1993-06-16 |
| AT390057B (en) | 1990-03-12 |
| JPS5815943A (en) | 1983-01-29 |
| IL66251A0 (en) | 1982-11-30 |
| DK154425C (en) | 1989-04-10 |
| IE53279B1 (en) | 1988-09-28 |
| IT8148817A0 (en) | 1981-07-03 |
| DK154425B (en) | 1988-11-14 |
| CH648546A5 (en) | 1985-03-29 |
| FR2510559A1 (en) | 1983-02-04 |
| SE8204117L (en) | 1983-01-04 |
| NL189666B (en) | 1993-01-18 |
| FR2510559B1 (en) | 1986-05-09 |
| ES8304064A1 (en) | 1983-03-01 |
| GB2101133A (en) | 1983-01-12 |
| GB2101133B (en) | 1985-08-14 |
| ES513658A0 (en) | 1983-03-01 |
| LU84244A1 (en) | 1983-01-20 |
| CA1186332A (en) | 1985-04-30 |
| ATA257382A (en) | 1989-08-15 |
| KR860001886B1 (en) | 1986-10-24 |
| NL8202677A (en) | 1983-02-01 |
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