DK154425B - Fremgangsmaade til fremstilling af carnitinchlorid - Google Patents
Fremgangsmaade til fremstilling af carnitinchlorid Download PDFInfo
- Publication number
- DK154425B DK154425B DK295482A DK295482A DK154425B DK 154425 B DK154425 B DK 154425B DK 295482 A DK295482 A DK 295482A DK 295482 A DK295482 A DK 295482A DK 154425 B DK154425 B DK 154425B
- Authority
- DK
- Denmark
- Prior art keywords
- carnitine
- chloride
- hydrochloride
- acid chloride
- chlorinating agent
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 7
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims description 19
- 229960004203 carnitine Drugs 0.000 claims description 18
- 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 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 12
- 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
- HKYGSMOFSFOEIP-UHFFFAOYSA-N dichloro(dichloromethoxy)methane Chemical compound ClC(Cl)OC(Cl)Cl HKYGSMOFSFOEIP-UHFFFAOYSA-N 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims 1
- 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 8
- 238000006243 chemical reaction Methods 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- JXXCENBLGFBQJM-FYZOBXCZSA-N [(2r)-3-carboxy-2-hydroxypropyl]-trimethylazanium;chloride Chemical compound [Cl-].C[N+](C)(C)C[C@H](O)CC(O)=O JXXCENBLGFBQJM-FYZOBXCZSA-N 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 150000004702 methyl esters Chemical class 0.000 description 6
- 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 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- PHIQHXFUZVPYII-UHFFFAOYSA-N carnitine Chemical compound C[N+](C)(C)CC(O)CC([O-])=O PHIQHXFUZVPYII-UHFFFAOYSA-N 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 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 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229960000678 carnitine chloride Drugs 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001277 beta hydroxy acids Chemical class 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- -1 carnitine methyl ester Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation 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
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000007017 scission Effects 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
- 239000007858 starting material Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOQGJRQKCIJIDB-UHFFFAOYSA-N tin;hydrochloride Chemical compound Cl.[Sn] JOQGJRQKCIJIDB-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- 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
- 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
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- 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
i
DK 154425 B
Opfindelsen angår en særlig fremgangsmåde til fremstilling af D,L-carnitinchlorid, (CHg) gN-C^-CH-C^-COCl.
Cl" OH
D,L-Carnitinchlorid er et bredt anvendeligt mellempro-5 dukt for fremstillingen af adskillige carnitinderIvater, f.eks. estere og amider, hvis terapeutiske egenskaber er kendt.
Carnitin, (CH^) ^“C^-CH-CELj-COOH, indeholder for-
OH
10 uden en carboxylgruppe en hydroxylgruppe, der som bekendt er følsom over for surt reaktionsmiljø.
Det er kendt, f.eks. som angivet i Bull. Soc.
Chim. Fr. (1960), 1196, at β-hydroxysyrer og estere deraf let fraspalter et molekyle .vånd i et surt miljø og så-15 ledes danner umættede forbindelser. I Biochim. Biophys.
Acta 137, 98-106 (1967) og 152, 559 (1968) angives fra-spaltning af vand fra carnitin at finde sted i surt miljø under opvarmning. I J. Biol. Chem. 237/12, 3628 (1962) angives dannelse af crotonoylbetain som biprodukt at fin-20 de sted ved opvarmning af carnitin i surt miljø.
Eftersom en carboxylsyre omdannes til syrechlorid under sure betingelser, kunne carnitinchlorering ikke forventes at finde sted uden forudgående beskyttelse af hydroxylgruppen med henblik på undgåelse af nedbrydning 25 af udgangsmaterialet og dannelsen af uønskede biprodukter. Dette bekræftes helt og holdent af, hvad der kan udledes af den kendte teknik. Fremstillingen af syrechlori-der af hydroxysubstituerede syrer, efter at hydroxyl-gruppen i forvejen er blevet beskyttet, er omtalt i J.
30 Org. Chem. 43/20, 3972 (1978). Specielt omtales chlore-ringen af β-hydroxysmørsyre (der er en 3-hydroxysyre ligesom carnitin), efter forudgående beskyttelse af hydro-xylgruppen med en acetylgruppe, i J. Am. Chem. Soc. 95, 4016 (1973).
35 Det har nu overraskende vist sig, at det er muligt at omdanne D,L-camitinhydrochlorid til syrechloridet af D,L- carnitin under opnåelse af udmærkede udbytter, uden dannelse af' fra et industrielt synspunkt uacceptable mængder 2
DK 154425B
biprodukt (især crotonoylbetain). Dette opnås ved at chlorere D,L-ærrdtinhydrochlorid uden forudgående beskyttelse af hydroxylgruppen (f.eks. ved omdannelse af hydroxylgrup-pen til en acetylgruppe som foreskrevet i den kendte 5 teknik), forudsat at der overholdes visse kritiske driftsbetingelser.
Det har vist sig, at det molære forhold mellem carnitin og chloreringsmiddel, reaktionstemperaturen og reaktionstiden er kritiske parametre, der påvirker om-10 dannelsen af D,L-carnitinhydrochlorid til det tilsvarrøde syrechlo-rid, og at værdierne af disse parametre må ligge inden for veldefinerede områder.
Fremgangsmåden ifølge opfindelsen til omdannelse af carnitinhydrochlorid til syrechloridet af carnitin er ejendonne-15 lig ved, at man chlorerer carnitinhydrochlorid med et chloreringsmiddel, udvalgt fra gruppen bestående af thio- · nylchlorid, dichlormethylether og oxalylchlorid, ved stuetemperatur under anvendelse af reaktionstider på mellem ca. 1,5 og ca. -12 timer, idet det molære forhold 20 mellem carnitin og chloreringsmiddel holdes mellem 1:1 og 1:3.
Af hensyn til opnåelse af høje udbytter ved omdannelsen af carnitinhydrochlorid til syrechloridet er det væsentligt, at den før nævnte temperatur og de før 25 nævnte reaktionstider overholdes strengt, eftersom selv mindre variationer medfører dannelse af bi produkter. Eksempelvis vil, når oxalylchlorid anvendes som chloreringsmiddel, en reaktionstid på 15 timer medføre næsten fuldstændig omdannelse af carnitinhydro-30 chlorid til crotonoylbetain.
Fremgangsmåden ifølge opfindelsen forklares nærmere i de efterfølgende eksempler 1,2 og 3.
Eksempel 1 (chloreringsmiddel: thionylchlorid).
35 2,25 cm^ (0,03 mol) SOC^ sattes til 1,98 g (0,01 mol) D,L-camitinhydrochlorid ved stuetemperatur. Efter 1 times forløb var solubiliseringen af stofferne fuldstændig og betragtedes 3
DK 154425 B
efter 1,5 time som afsluttet. Overskuddet af SOCI2 af-destilleredes, og remanensen, bestående af syrechloridet af carnitin, vaskedes med vandfri ethylether. Med henblik på identifikation omdannedes syrechloridet til meth-5 ylesteren: reaktionsblandingen afkøledes til Q°C, og 10 cm vandfri methanol tilsattes dråbevis. Den resulterende blanding koncentreredes derpå i vakuum ved 35-40°C, hvorved der opnåedes et gelatinøst råprodukt, som ved tørring i vakuum størknede, men forblev meget hygrosko-10 pisk.
T.L.C. chloroform 55/ methanol 35/ H^O 5 / NH^QH 5 NMR-spektrum D20-opløsningsmiddel 4,82 (IH, m, -CH-); 3,83 (3H, s, -OCH3); 3,55 (2H, d, 15 OH CH3 —>i-CH2-); 3,30 (9H, s, -&4cH3); 2,73 (2H, d, -CH2CO-) CH3
Elementaranalyse:
Beregnet Fundet 20 C 45,39 43,99 K.F^ 4% H 8,57 8,54 N 6,62 6,09
Cl 16,75 16,92 $) 25 K.F. står for Karl Fischer, og nærmere angivet er der tale om Karl Fischers velkendte metode til bestemmelse af vand.
Eksempel 2 (chloreringsmiddel: dichlormethylether) 30 Der anvendtes samme fremgangsmåde som i det fore gående eksempel med undtagelse af, at der i stedet for 3 thionylchlorid anvendtes dichlormethylether (1,78 cm ; 0,02 mol). Reaktionsblandingen henstilledes natten over ved stuetemperatur. Overskuddet af dichlormethylether 35 afdestilleredes, og remanensen vaskedes med vandfri ethylether. Remanensen viste sig at bestå af syrechloridet af carnitin.
DK 154425B
4 CHv NMR CD3NC S 3,33 (9H, S, j CHf 3,36-3,60 (4H, m, >A-CH2-, -CH2COCl) ; 5 4,40-4,90 (IH, m, -CH-)
OH
Efter udveksling med D20 antog de kemiske forskydninger samme værdier som forskydningerne i NMR-spektret for carnitin. Det rå syrechlorid omdannedes derpå til 10 methylesteren som tidligere beskrevet. Methylesteren af carnitin viste de.til det tidligere isolerede produkt svarende kemisk-fysiske egenskaber.
Eksempel 3 (chloreringsmiddel: oxalylchlorid) 15 Der anvendtes samme fremgangsmåde som i det fo regående eksempel med undtagelse af, at der i stedet 3 for dichlormethylether anvendtes oxalylchlorid (2,6 cm ; 0,01 mol). Reaktionsblandingen holdtes under omrøring ved 25°C i 4 timer. Overskuddet af chloreringsmiddel af-20 destilleredes. Remanensen vaskedes med vandfri ethyl-ether. Med henblik på identifikation omdannedes syre-chloridet til det methylester som tidligere beskrevet.
Methylesteren af carnitin viste de til det tidligere isolerede produkt svarende kemisk-fysiske egenska-25 ber.
De efterfølgende eksempler A og B tilsigter at illustrere, at de i det foregående nævnte driftsbetin- gelser absolut må overholdes for at opnå syrechloridet af carnitin.
30
Eksempel A (den rigtige reaktionstemperatur overholdes ikke).
En blanding af camitinhydrochlorid og. thicnylchlorid (molforhold 1:1) holdtes under omrøring ved 50°C. Prøver 35 blev udtaget fra reaktionsblandingen efter forløbet af 0,5 time, 1 time og 1,5 time fra reaktionens begyndelse. Prøverne undersøgtes ved TLC (chloroform 55/ CH^OH 35/ H20 5/ NH^OH 5) efter fortynding med methanol for at
DK 154425 B
5 omdanne det eventuelt tilstedeværende syrechlorid til methylesteren.
Efter 0,5 time noteredes tilstedeværelse af camitin-hydrochlcrid og iæthylester af catnitin (r^ henholdsvis 0,4 og 5 0,8).
Efter 1 time begyndte crotonoylbetain, carnitin-hydrochlorid og carnitin-methylester (Rf henholdsvis 0,2, 0,4 og 0,8) at dannes.
Efter 1,5 time noteredes tilstedeværelse af croto-10 noylbetain sammen med andre nedbrydningsprodukter, der ikke kunne identificeres.
Eksempel B (den rigtige reaktionstid overholdtes ikke).
15 2,3 cm^ (0,03 mol) thionylchlorid sattes til 1,98 g (0,01 mol) carnitin-hydrochlorid, og den dannede reaktionsblanding holdtes under omrøring ved stuetemperatur i 24 timer. Overskydende thionylchlorid afdestilleredes, og den rå remanens vaskedes med vandfri ethylether, hvor-20 ved der opnåedes et fast produkt med et smp. på 217-218°C.
TLC chloroform 55/ methanol 35/ H20 5/ NH^OH 5/ 0,2 NMR D20 (5 7,2-6,2 (2H, m, -CH=CH-) ; 4,2 (2H, d, >Å-CH2-); CH3 3,2 (9H, s, CHg^Si-y 25 αζ
Som det fremgår af TLC og NMR-spektret, dannes syrechloridet af carnitin ikke under disse reaktionsbetingelser. Tværtimod foregår der en fraspaltning af vand under dannelse af crotonoylbetain 30 ch3 CH3^-CH2 -ch=ch-cooh ch3/
Claims (1)
- DK 154425 B Fremgangsmåde til fremstilling af syrechloridet af carnitin, kendetegnet ved, at man chlore-rer carnitinhydrochlorid med et chloreringsmiddél, udvalgt fra gruppen bestående af thionylchlorid, dichlor-5 methylether og oxalylchlorid, ved stuetemperatur under anvendelse af reaktionstider mellem ca. 1,5 og ca. 12 timer, idet det molære forhold mellem carnitin og chlorerings-middel holdes mellem 1:1 og 1:3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT48817/81A IT1171360B (it) | 1981-07-03 | 1981-07-03 | Procedimento per la preparazione del cloruro acido di carnitina |
| IT4881781 | 1981-07-03 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK295482A DK295482A (da) | 1983-01-04 |
| DK154425B true DK154425B (da) | 1988-11-14 |
| DK154425C DK154425C (da) | 1989-04-10 |
Family
ID=11268676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK295482A DK154425C (da) | 1981-07-03 | 1982-06-30 | Fremgangsmaade til fremstilling af carnitinchlorid |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS5815943A (da) |
| KR (1) | KR860001886B1 (da) |
| AT (1) | AT390057B (da) |
| BE (1) | BE893713A (da) |
| CA (1) | CA1186332A (da) |
| CH (1) | CH648546A5 (da) |
| DE (1) | DE3224666A1 (da) |
| DK (1) | DK154425C (da) |
| ES (1) | ES8304064A1 (da) |
| FR (1) | FR2510559B1 (da) |
| GB (1) | GB2101133B (da) |
| GR (1) | GR76546B (da) |
| IE (1) | IE53279B1 (da) |
| IL (1) | IL66251A0 (da) |
| IT (1) | IT1171360B (da) |
| LU (1) | LU84244A1 (da) |
| NL (1) | NL189666C (da) |
| SE (1) | SE448724B (da) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1190358B (it) * | 1985-05-24 | 1988-02-16 | Sclavo Spa | Procedimento per la preparazione di 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 (it) * | 1979-04-23 | 1986-02-10 | Sigma Tau Ind Farmaceuti | Esteri e ammidi di acil carnitine loro procedimenti di preparazione e loro uso terapeutico |
| DE2943433A1 (de) * | 1979-10-26 | 1981-05-07 | Bayer Ag, 5090 Leverkusen | Verfahren zur herstellung von carbonsaeurehalogeniden |
-
1981
- 1981-07-03 IT IT48817/81A patent/IT1171360B/it active
-
1982
- 1982-06-24 CH CH3884/82A patent/CH648546A5/it 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 BE BE0/208502A patent/BE893713A/fr not_active IP Right Cessation
- 1982-06-30 DK DK295482A patent/DK154425C/da not_active IP Right Cessation
- 1982-06-30 LU LU84244A patent/LU84244A1/fr unknown
- 1982-06-30 CA CA000406463A patent/CA1186332A/en not_active Expired
- 1982-07-01 KR KR8202945A patent/KR860001886B1/ko active
- 1982-07-01 DE DE19823224666 patent/DE3224666A1/de active Granted
- 1982-07-01 GR GR68615A patent/GR76546B/el unknown
- 1982-07-02 ES ES513658A patent/ES8304064A1/es not_active Expired
- 1982-07-02 FR FR8211685A patent/FR2510559B1/fr not_active Expired
- 1982-07-02 SE SE8204117A patent/SE448724B/sv not_active IP Right Cessation
- 1982-07-02 JP JP57116084A patent/JPS5815943A/ja active Granted
- 1982-07-02 AT AT0257382A patent/AT390057B/de not_active IP Right Cessation
- 1982-07-02 NL NLAANVRAGE8202677,A patent/NL189666C/xx not_active IP Right Cessation
- 1982-07-07 IL IL66251A patent/IL66251A0/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NL189666B (nl) | 1993-01-18 |
| GB2101133A (en) | 1983-01-12 |
| GB2101133B (en) | 1985-08-14 |
| ATA257382A (de) | 1989-08-15 |
| ES513658A0 (es) | 1983-03-01 |
| FR2510559B1 (fr) | 1986-05-09 |
| DE3224666A1 (de) | 1983-01-20 |
| KR860001886B1 (ko) | 1986-10-24 |
| CH648546A5 (it) | 1985-03-29 |
| IT8148817A0 (it) | 1981-07-03 |
| NL8202677A (nl) | 1983-02-01 |
| DK154425C (da) | 1989-04-10 |
| SE448724B (sv) | 1987-03-16 |
| IL66251A0 (en) | 1982-11-30 |
| LU84244A1 (fr) | 1983-01-20 |
| FR2510559A1 (fr) | 1983-02-04 |
| GR76546B (da) | 1984-08-10 |
| AT390057B (de) | 1990-03-12 |
| ES8304064A1 (es) | 1983-03-01 |
| JPH0244300B2 (da) | 1990-10-03 |
| CA1186332A (en) | 1985-04-30 |
| NL189666C (nl) | 1993-06-16 |
| DE3224666C2 (da) | 1991-01-24 |
| SE8204117D0 (sv) | 1982-07-02 |
| IT1171360B (it) | 1987-06-10 |
| BE893713A (fr) | 1982-10-18 |
| KR840000475A (ko) | 1984-02-22 |
| IE821524L (en) | 1983-01-03 |
| JPS5815943A (ja) | 1983-01-29 |
| DK295482A (da) | 1983-01-04 |
| IE53279B1 (en) | 1988-09-28 |
| SE8204117L (sv) | 1983-01-04 |
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