KR860001886B1 - Process for the preparation of carnitine chloride - Google Patents
Process for the preparation of carnitine chloride Download PDFInfo
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- KR860001886B1 KR860001886B1 KR8202945A KR820002945A KR860001886B1 KR 860001886 B1 KR860001886 B1 KR 860001886B1 KR 8202945 A KR8202945 A KR 8202945A KR 820002945 A KR820002945 A KR 820002945A KR 860001886 B1 KR860001886 B1 KR 860001886B1
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- PHIQHXFUZVPYII-UHFFFAOYSA-N carnitine Chemical compound C[N+](C)(C)CC(O)CC([O-])=O PHIQHXFUZVPYII-UHFFFAOYSA-N 0.000 title claims description 8
- 229960000678 carnitine chloride Drugs 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 3
- 229960004203 carnitine Drugs 0.000 claims description 25
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 14
- 239000012320 chlorinating reagent Substances 0.000 claims description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000005660 chlorination reaction Methods 0.000 claims description 5
- 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 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical class C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 20
- 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
- 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 description 7
- 239000002253 acid Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 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
- 150000001805 chlorine compounds Chemical class 0.000 description 5
- -1 for example Chemical class 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 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
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 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
- 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 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000009118 appropriate response Effects 0.000 description 1
- 150000001277 beta hydroxy acids Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035945 sensitivity 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
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- 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
- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
내용 없음.No content.
Description
본 발명은 D,L-염화카르니틴
D,L-염화카르니틴은 그 치료적인 특성이 알려진 예컨대 에스테르 및 아미드와 같은 수종의 카르니틴 유도체들의 제조를 위한 전반적인 중간체이다.D, L-carnitine chloride is an overall intermediate for the preparation of several carnitine derivatives such as, for example, esters and amides whose therapeutic properties are known.
카르니틴
예컨대, 1970년 발행, Bull. Soc. Chim. Fr. 제 1196면에 공개된 바와 같이 β-히드록시산과 이것의 에스테르는 산환경에서 물분자를 용이하게 유리시켜 불포화 화합물을 생성한다는 것은 실제에 있어서 알려져 있는 것이다.See, eg, 1970. Bull. Soc. Chim. Fr. As disclosed on page 1196, it is known in practice that β-hydroxy acids and their esters readily release water molecules in an acidic environment to produce unsaturated compounds.
Biochim. Biophys. Acta 1967년 발행, 137권 98내지 106면 및 1968년 발행 152권 559면에 카르니틴 탈수가 가열하의 산성환경에서 일어나는 것이 공개되어 있다. 1962년 발행 J. BioI. Chem. 237권 12의 3268면에는 부산물로서의 크로토노일베타인의 생성이 산성환경에서 카르니틴을 가열하면 일어난다는 것을 공개하고 있다. 카르복시산은 산성조건에서 산염화물로 전환되기 때문에 카르니틴 염소화는 출발물질의 감성과 바람직하지 못한 부산물의 생성을 피할 목적으로 히드록실기를 미리 보호하지 않고는 기대할 수 없는 것이다.Biochim. Biophys. Acta 1967, pp. 137, 98-106, and 1968, pp. 152, 559 disclose that carnitine dehydration occurs in an acidic environment under heating. 1962 J. BioI. Chem. Page 3268, Vol. 237, 12, discloses that the production of crotonoylbetaine as a byproduct occurs when carnitine is heated in an acidic environment. Since carboxylic acids are converted to acid chlorides under acidic conditions, carnitine chlorination cannot be expected without protecting the hydroxyl groups in advance in order to avoid the sensitivity of the starting materials and the formation of undesirable by-products.
전술한 공개는 종래의 기술에 의해서 추론될 수 있는 것에 의해서 완전히 확인된다. 히드록실기가 미리보호된 후에 히드록시 치환산의 산염화물을 제조한다는 것은 1978년 발행 J. Org. Chem. 43권 20의 3972면에 공개되어 있다. 보다 상세히 설명하면, 아세틸기로 히드록실기를 미리 보호한 후의 β-히드록시부티르산(카르니틴인 β-히드록시산)의 염소화는 1973년 발행, J. Am. Chem. Soc. 95권 4106면에 공개되어 있다.The foregoing disclosure is fully confirmed by what can be inferred by the prior art. The preparation of acid chlorides of hydroxy substituted acids after the hydroxyl groups have been preprotected is described in J. Org. Chem. 43, 20, published on page 3972. In more detail, chlorination of β-hydroxybutyric acid (carnitine β-hydroxy acid) after protecting the hydroxyl group in advance with an acetyl group was published in 1973, J. Am. Chem. Soc. 95, published on page 4106.
놀랍게도 D,L-카르니틴이 산업적 견지로 보아 받아드릴 수 없는 량의 부산물(특히 크로토노일벤타인)을 생성함이 없이 우수한 수율로 얻을 수 있는 D,L-염화카르니틴 산으로 전환될 수 있다는 것이 현재 알려져 있다. 이는 히드록실기를 미리 보호하지 않고 D,L-카르니틴을 염소화하여 서이루어진다(예컨대, 종래기술에 의해서 히드록실기를 아세틸기로 전환시켜서). 그러나 약간의 임계 작업조건들이 수반된다.Surprisingly, it is possible that D, L-carnitine can be converted to D, L-carnitine acid, which can be obtained in excellent yields without producing an unacceptable amount of by-products (especially crotonoylbentine). Currently known. This is accomplished by chlorination of D, L-carnitine without prior protection of the hydroxyl groups (eg by converting hydroxyl groups to acetyl groups by conventional techniques). However, some critical working conditions are involved.
실제에 있어서 카르니틴/염소화제의 몰비, 반응온도 및 반응시간은 D,L-카르니틴을 대응하는 산염화물로 전환하는데 영향을 주는 임계변수들이고 또 전술한 변수들의 값이 명확한 범위내로 떨어져야 한다는 것은 알려져 있는 것이다.In practice, it is known that the molar ratio, reaction temperature and reaction time of carnitine / chlorinating agent are the critical parameters affecting the conversion of D, L-carnitine to the corresponding acid chlorides and that the values of the above mentioned parameters should fall within a certain range. .
본 발명에 의하면, 카르니틴을 카르니틴의 산염화물로 전환시키는 것은 다음의 공정들을 포함한다.According to the present invention, the conversion of carnitine to an acid chloride of carnitine includes the following steps.
카르니틴을 염소화제(호적하게는 염화티오닐, 디클로로메틸에테르 및 옥살일클로라이드에서 선택된)로 약 1.5내지 12시간 사이의 반응시간 동안 실온으로 염소화하는 것. 펜타염화인은 또한 염소화제로 사용될수 있다. 그러나, 이 염화제는 위에서 지적한 것들과 비교하면 현저히 많은 반응시간(1내지 3일)이 소요된다는 점에서 바람직하지 못하다.Chlorination of carnitine to room temperature with a chlorinating agent (preferably selected from thionyl chloride, dichloromethylether and oxalyl chloride) for a reaction time between about 1.5 and 12 hours. Phosphorus pentachloride can also be used as a chlorinating agent. However, these chlorides are undesirable in that they require significantly longer reaction times (1 to 3 days) compared to those pointed out above.
호적하게는 카르니틴/염소화제의 몰비는 1 : 1 및 1 : 3의 사이이다. 카르니틴을 산염화물로 전환하는 데 있어서 높은 수율로 얻는다는 견지에서 보면 적은 변화라도 부산물 생성을 유발하기 때문에 전술한 온도와 반응시간을 엄격히 이행하는 것이 필수적이다. 예컨대, 염화옥살일이 염소화제로 사용될 때에는 15시간의 반응시간으로 대체로 카르니틴을 크로토노일베타인으로 완전히 감성하게 된다.Preferably the molar ratio of carnitine / chlorinating agent is between 1: 1 and 1: 3. In terms of obtaining high yields in the conversion of carnitine to acid chlorides, it is essential to strictly implement the above-mentioned temperatures and reaction times, as even small changes cause by-product generation. For example, when oxalyl chloride is used as a chlorinating agent, a reaction time of 15 hours generally causes carnitine to be completely sensitized to crotonoyl betaine.
다음의 실시예 1 및 2는 본 발명의 방법을 비제한적으로 설명하는 것이다.Examples 1 and 2 which follow illustrate the method of the invention without limitation.
[실시예 1]Example 1
(염소화제 : 염화티오닐)(Chlorinating agent: thionyl chloride)
2.25cc(0.03몰)의 SOCl2를 1.98g(0.01몰)의 D,L-염산카르니틴에 첨가하였다. 1시간 후에 가용화는 완전하였고 또 1.5시간 후에는 종료되었다. 과잉량 SOCl2는 증류 제거하고 카르니틴 산염화물을 함유하고 있는 잔류물은 무수에틸에테르로 세척하였다. 확인할 목적으로 산염화물을 에틸에테르로 전환시켰다. 반응혼합물을 0℃에 냉각시키고 또 10cc의 무수메탄올을 적가하였다. 이어서 이같이 된 혼합물을 35내지 40℃에서 진공하에 농축시켰다. 이리하여 진공하에 건조되고 고체화 되지만 극히 흡수성으로 잔류하는 고상조 생성물을 얻었다.2.25 cc (0.03 mol) of SOCl 2 was added to 1.98 g (0.01 mol) of D, L-carnitine hydrochloride. Solubilization was complete after 1 hour and terminated after 1.5 hours. Excess SOCl 2 was distilled off and the residue containing carnitine acid chloride was washed with anhydrous ethyl ether. The acid chloride was converted to ethyl ether for identification purposes. The reaction mixture was cooled to 0 ° C. and 10 cc of anhydrous methanol was added dropwise. The resulting mixture was then concentrated in vacuo at 35-40 ° C. This gave a solidified product which dried under vacuum and solidified but remained extremely absorbent.
T,L,C, 클로로포름55/ 메탄올5/ NH4OH 5 NMR 스펙트럼 D2O 용매T, L, C, Chloroform 55 / Methanol 5 / NH 4 OH 5 NMR Spectrum D 2 O Solvent
원소분석Elemental analysis
이론 실제Theory actual
C 45.39 43.99 K.F.~4%C 45.39 43.99 K.F. ~ 4%
H 8.57 8.54H 8.57 8.54
N 6.62 6.09N 6.62 6.09
C1 16.75 16.92C1 16.75 16.92
[실시예 2](염소화제 : 디클로로메틸에테르)Example 2 (chlorinating agent: dichloromethyl ether)
전술한 실시예의 방법을 사용하였다. 단 염화티오닐 대신에 디클로로메틸에테르(1.78cc; 0.02몰)를 사용하였다. 반응혼합물을 실온에 하룻밤 동안 방치하였다. 과잉량 디클로메틸에테르는 증류 제거하고 또 잔류물은 무수에틸에테르로 세척하였다. 잔류물은 카르니틴 산염화물이 포함되어 있음을 알았다.The method of the above described example was used. Dichloromethyl ether (1.78 cc; 0.02 mol) was used instead of thionyl chloride. The reaction mixture was left at room temperature overnight. Excess dichloromethyl ether was distilled off and the residue was washed with anhydrous ethyl ether. It was found that the residue contained carnitine acid chloride.
D2O로 교환한 후에 그 화학적 이동은 카르니틴의 NMR 스펙트럼의 값과 동일한 값을 회복시켰다. 그 결과 조산염화물은 전술한 바와 같이 메틸에스테르로 전환하였다. 카르니틴 메틸에스테르는 전술한 단리생성물에 대응하는 화학-물리적 특성들을 보였다.After exchange with D 2 O, the chemical shift restored the same value as the NMR spectrum of carnitine. As a result, the crude acid salt was converted into methyl ester as described above. Carnitine methylester showed chemical-physical properties corresponding to the above-mentioned isolated product.
다음의 실시예 A와 B는 전술한 작업조건들이 카르니틴 산염화물을 얻기위해서 절대로 이행되어야 한다는 것을 설명하는 것이 목적인 것이다.The following Examples A and B are intended to illustrate that the above operating conditions must be fulfilled in order to obtain carnitine acid chloride.
[실시예 A]Example A
(적온이 적용되지 않는다)(Temperature does not apply)
카르니틴과 염화티오닐(몰비 1 : 1)의 혼합물을 50℃에서 교반하였다. 반응혼합물의 시료를 반응개시로 부터 0.5시간, 1시간 및 1.5시간 후에 끝냈다. 시료를 산염화물을 약간이라도 메틸에스테르로 전환시키기 위해서 메탄올로 희석한 후에 TLC (클로로포름 55/ CH3OH 35/ H2O 5/ NH4OH 5)로 검사하였다. 0.5시간 후에 카르니틴과 카르니틴메틸에스테르의 존재(각각 Rf0.4와 0.8)를 확인하였다. 1시간 후에 크로토노일베타인, 카르니틴 및 카르니틴메틸에스테르(각각 Rf0.2-0, 4-0.8)가 생성하기 시작하였다. 1.5시간 후에 크로토노일베타인과 확인할 수 없는 다른 감성생성물들의 존재를 확인하였다.A mixture of carnitine and thionyl chloride (molar ratio 1: 1) was stirred at 50 ° C. Samples of the reaction mixture were finished 0.5 hours, 1 hour and 1.5 hours after the start of the reaction. Samples were diluted with methanol to convert the acid chloride to methyl ester even slightly and then examined by TLC (chloroform 55 / CH 3 OH 35 / H 2 O 5 / NH 4 OH 5). After 0.5 hours, the presence of carnitine and carnitine methyl ester (R f 0.4 and 0.8, respectively) was confirmed. After 1 hour crotonoylbetaine, carnitine and carnitine methylester (R f 0.2-0, 4-0.8, respectively) began to form. After 1.5 hours the presence of crotonoylbetaine and other unidentifiable emotional products was confirmed.
[실시예 B]Example B
(적당한 반응시간이 적용되지 않는다)(Appropriate response time does not apply)
염화티오닐(2.3cc; 0.03몰)을 염산카르니틴(1.98cc; 0.01몰)에 첨가하여서 된 반응혼합물을 실온에서 24시간 교반하였다. 과잉량의 염화티오닐을 증류 제거하여 그 조잔류물을 무수에틸에테르로 세척하였다. 이리하여 융점 217-218℃의 고체 생성물을 얻었다.The reaction mixture obtained by adding thionyl chloride (2.3 cc; 0.03 mol) to carnitine hydrochloride (1.98 cc; 0.01 mol) was stirred at room temperature for 24 hours. Excess thionyl chloride was distilled off and the crude residue was washed with anhydrous ethyl ether. This gave a solid product having a melting point of 217-218 ° C.
TLC 클로로포름 55/ 메탄올 35/ H2O 5/ NH4OH 5/ Rf0.2TLC chloroform 55 / methanol 35 / H 2 O 5 / NH 4 OH 5 / R f 0.2
TLC 및 NMR 스펙트럼이 표시하는 바와 같이, 이들 반응 조건에서는 카르니틴의 산염화물은 생성하지 않는다. 반대로 크로토노일베타인 생성As indicated by the TLC and NMR spectra, no acid chloride of carnitine is produced under these reaction conditions. Conversely produce crotonoylbetaine
으로 탈수가 일어난다.Dehydration takes place.
Claims (2)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT48817 | 1981-07-03 | ||
| IT48817/81A IT1171360B (en) | 1981-07-03 | 1981-07-03 | PROCEDURE FOR THE PREPARATION OF CARNITINE ACID CHLORIDE |
| IT48817A/81 | 1981-07-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR840000475A KR840000475A (en) | 1984-02-22 |
| KR860001886B1 true KR860001886B1 (en) | 1986-10-24 |
Family
ID=11268676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR8202945A KR860001886B1 (en) | 1981-07-03 | 1982-07-01 | Process for the preparation of 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) | ES8304064A1 (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 |
-
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 CA CA000406463A patent/CA1186332A/en not_active Expired
- 1982-06-30 BE BE0/208502A patent/BE893713A/en not_active IP Right Cessation
- 1982-06-30 DK DK295482A patent/DK154425C/en not_active IP Right Cessation
- 1982-06-30 LU LU84244A patent/LU84244A1/en unknown
- 1982-07-01 GR GR68615A patent/GR76546B/el unknown
- 1982-07-01 KR KR8202945A patent/KR860001886B1/en active
- 1982-07-01 DE DE19823224666 patent/DE3224666A1/en active Granted
- 1982-07-02 ES ES513658A patent/ES8304064A1/en not_active Expired
- 1982-07-02 FR FR8211685A patent/FR2510559B1/en not_active Expired
- 1982-07-02 AT AT0257382A patent/AT390057B/en not_active IP Right Cessation
- 1982-07-02 SE SE8204117A patent/SE448724B/en not_active IP Right Cessation
- 1982-07-02 NL NLAANVRAGE8202677,A patent/NL189666C/en not_active IP Right Cessation
- 1982-07-02 JP JP57116084A patent/JPS5815943A/en active Granted
- 1982-07-07 IL IL66251A patent/IL66251A0/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE8204117L (en) | 1983-01-04 |
| BE893713A (en) | 1982-10-18 |
| ES513658A0 (en) | 1983-03-01 |
| JPH0244300B2 (en) | 1990-10-03 |
| DE3224666A1 (en) | 1983-01-20 |
| DK154425C (en) | 1989-04-10 |
| FR2510559A1 (en) | 1983-02-04 |
| KR840000475A (en) | 1984-02-22 |
| GR76546B (en) | 1984-08-10 |
| LU84244A1 (en) | 1983-01-20 |
| AT390057B (en) | 1990-03-12 |
| CH648546A5 (en) | 1985-03-29 |
| SE448724B (en) | 1987-03-16 |
| ATA257382A (en) | 1989-08-15 |
| DE3224666C2 (en) | 1991-01-24 |
| IE53279B1 (en) | 1988-09-28 |
| CA1186332A (en) | 1985-04-30 |
| NL8202677A (en) | 1983-02-01 |
| ES8304064A1 (en) | 1983-03-01 |
| IE821524L (en) | 1983-01-03 |
| GB2101133A (en) | 1983-01-12 |
| IT1171360B (en) | 1987-06-10 |
| IT8148817A0 (en) | 1981-07-03 |
| DK154425B (en) | 1988-11-14 |
| JPS5815943A (en) | 1983-01-29 |
| SE8204117D0 (en) | 1982-07-02 |
| NL189666C (en) | 1993-06-16 |
| FR2510559B1 (en) | 1986-05-09 |
| IL66251A0 (en) | 1982-11-30 |
| DK295482A (en) | 1983-01-04 |
| NL189666B (en) | 1993-01-18 |
| GB2101133B (en) | 1985-08-14 |
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