- Preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as starting material
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The invention discloses a preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as a starting material, and belongs to the field of medicinal chemistry. The method comprises the steps: using R-(-)-epoxychlorohydrin and hydrocyanic acid as starting materials, performing a reaction for synthesis of R-4-chloro-3-hydroxybutyronitrile under the action of a basic catalyst, thensynthesizing L-carnitine hydrochloride through two routes, purifying the L-carnitine hydrochloride prepared through the two routes further through resin so as to remove chloride ions, and preparing the final product L-carnitine. The two process routes are simple, the reaction conditions are mild, the operation is simple and feasible, and industrial production is convenient; the whole process is green and environmentally friendly, the reaction yield is high, three waste is little, no sodium cyanide is used, and no solid waste sodium salt is generated; and the hydrolysis by-product ammonium chloride has good quality, and can be sold as a by-product, and great economic benefits and market competitiveness are achieved.
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Paragraph 0078-0093
(2019/11/12)
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- Synthesis method of L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine
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The invention discloses a synthesis method of L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine. The synthesis method is characterized in that: (R)-epichlorohydrin serves as a starting material; the (R)-epichlorohydrin is firstly subjected to a ring-opening reaction by gaseous hydrogen cyanide; L-(-)-4-chlorine-3-hydroxybutyronitrile is obtained; then the L-(-)-4-chlorine-3-hydroxybutyronitrile is aminated by trimethylamine; and the L-(-)-chlorination 3-cyano-2-propyltrimethylamine is obtained. After the ring-opening reaction is completed, a small amount of hydrogen cyanide dissolved in a material needs to be replaced with nitrogen, and an end point is that a benzidine-cupric acetate test paper does not change to blue. According to the synthesis method, thegaseous hydrogen cyanide is firstly used to open a ring, and then the trimethylamine is used to perform amination, therefore the L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine with high yield and high content can be obtained; and by adopting the gaseous hydrogen cyanide to open the ring, only the nitrogen is needed to replace the gaseous hydrogen cyanide after the ring-opening reaction, the subsequent recovery of the trimethylamine is not affected, and the post-treatment process is greatly simplified.
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Paragraph 0036; 0037
(2018/09/21)
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- Novel method for preparing L-carnitine
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The invention discloses a novel method for preparing L-carnitine and belongs to the technical field of medication chemistry. The method disclosed by the invention comprises the following steps: reacting quinine I and trimethylchlorosilane, thereby obtaining a quinine derivative II; reacting the quinine derivative II with racemic epoxy chloropropane, thereby obtaining quinine derivative quaternary ammonium salt III; reacting the quinine derivative quaternary ammonium salt III with a cyanide inorganic salt, and performing chiral ring opening to generate (R)-2-hydroxynitrile quaternary ammonium salt IV; carrying out an ion exchange reaction between the (R)-2-hydroxynitrile quaternary ammonium salt IV and trimethylamine, thereby obtaining (R)-2-hydroxynitrile trimethylamine salt, performing acidic hydrolysis, and performing ion exchange desalination, thereby obtaining the L-carnitine. The method provided by the invention is simple and feasible, the yield is greatly improved, and residues of heavy metal ions are avoided.
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Paragraph 0019; 0020; 0021
(2017/08/27)
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- Practical and efficient utilisation of (R)-3-chloro-1,2-propanediol in synthesis of L-carnitine
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As a by-product originating from Salen Co(III) catalysed hydrolytic kinetic resolution (HKR) of (±)-epichlorohydrin in the manufacturing procedure of L-Carnitine, (R)-3-chloro-1,2-propanediol was utilised as a starting chiral material to prepare via key nitrile intermediates and by a final hydrolysis L-Carnitine. The new synthetic approach demonstrated an efficient utilisation of the by-product.
- Yang, Yunxu,Wang, Weili,Wumaier, Aikeremu,Sheng, Ruilong,Zhang, Xuetao,Zhang, Tianyi
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experimental part
p. 371 - 372
(2011/10/09)
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- Asymmetric synthesis of l-carnitine from (R)-3-chloro-1,2-propanediol
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A practical chemical synthesis of l-carnitine (1) has been accomplished from (R)-3-chloro-1,2-propanediol ((R)-4), which is a main by-product originated from (R,R)-Salen Co(III) catalyzed hydrolytic kinetic resolution (HKR) of (±)-epichlorohydrin. (R)-4 was utilized as a chiral starting material to prepare the key intermediate cyclic sulfite ((R)-5). The new synthetic approach demonstrated an efficient utilization of organic by-product for the asymmetric synthesis of bioactive compounds.
- Li, Xu Qin,Yang, Yun Xu,Wang, Wei Li,Hu, Bin,Xue, Hui Min,Zhang, Tian Yi,Zhang, Xue Tao
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body text
p. 765 - 767
(2012/01/03)
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- A PREPARATION METHOD OF HIGH-PURITY L-CARNITINE
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The present invention relate to a preparation method of high-purity L-carnitine which belongs to an important technique of qulity control in different steps of chiral medicine production. The method comprises the following steps of :monitoring the content of the L-isomer impurity in chiral material S-epichlorohydrin by gas chromatography and chiral cilumn and controlling the content of the L-isomer impurity in chiral raw material in the definite range; monitoring and controlling the specific optical rotation of the chiral intermediate L-3-chloro-2-hydroxy-N,N,N-trimethyl-propanaminium in the definite ranges using a polarimeter; monitoring the content of the R-isomer in the intermediate L-3-cyano-2-hydroxy-N,N,N-trimethyl-propanaminium using derivation agent (+)α-methyl-6-methoxy-2-naphthaleneaceyl chloride by HPLC and controlling the content of the isomer in the intermediate in the definite range; and measuring the final product L-carnitine using derviation agent (+)α-methyl-6-methoxy-2-naphthaleneaceyl chloride by HPLC. This method gives the high-purity L-carnitine in which the content of L-isomer may be more than 97% and that of R-isomer less than 2%.
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Page/Page column 8
(2011/09/15)
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- PREPARATION METHOD OF HIGH-PURITY L-CARNITINE
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The present invention relate to a preparation method of high-purity L-carnitine which belongs to an important technique of quality control in different steps of chiral medicine production. The method comprises the following steps of: monitoring the content of the L-isomer impurity in chiral material S-epichlorohydrin by gas chromatography and chiral column and controlling the content of the L-isomer impurity in chiral raw material in the definite range; monitoring and controlling the specific optical rotation of the chiral intermediate L-3-chloro-2-hydroxy-N,N,N-trimethyl-propanaminium in the definite ranges using a polarimeter; monitoring the content of the R-isomer in the intermediate L-3-cyano-2-hydroxy-N,N,N-trimethyl-propanaminium using derivation agent (+)α-methyl-6-methoxy-2-naphthaleneaceyl chloride by HPLC and controlling the content of the isomer in the intermediate in the definite range; and measuring the final product L-carnitine using derviation agent (+)α-methyl-6-methoxy-2-naphthaleneaceyl chloride by HPLC. This method gives the high-purity L-carnitine in which the content of L-isomer may be more than 97% and that of R-isomerless than 2%.
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Page/Page column 5
(2011/11/06)
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- Short and Practical Syntheses of (R)-(-)-Carnitine and (R)-(-)-γ-Amino-β-hydroxybutyric Acid (GABOB)
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Short and practical syntheses of (R)-(-)-carnitine and (R)-(-)-γ-amino-β-hydroxybutyric acid have been developed, both commencing with the catalytic asymmetric dihydroxylation of allyl bromide.
- Kolb, Hartmuth C.,Bennani, Youssef L.,Sharpless, K. Barry
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p. 133 - 141
(2007/10/02)
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- An efficient synthesis of (R)-carnitine
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An efficient synthesis of (R)-carnitine hydrochloride is described. The starting material is obtained by microbial resolution of (RS)-2,3-dichloro-1-propanol.
- Kasai,Sakaguchi
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p. 1211 - 1212
(2007/10/02)
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