1116-95-6

Usage

InChI:InChI=1/C7H15N2O/c1-9(2,3)6-7(10)4-5-8/h7,10H,4,6H2,1-3H3/q+1/t7-/m0/s1

Upstream product

• 105-33-9 4-chloro-3-hydroxybutyronitrile 
• 75-50-3 trimethylamine 
• 773837-37-9 sodium cyanide 
• 101396-91-2 N-(3-chloro-2-hydroxypropyl)trimethylammonium chloride 
• 18933-33-0 (R,S)-carnitinenitrile chloride 
• 74-90-8 hydrogen cyanide 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 67843-74-7 (S)-epichlorohydrin 
• 84367-31-7 (R)-γ-chloro-β-hydroxybutyronitrile 
• 593-81-7 trimethylamine hydrochloride 
• 101396-91-2 (S)-N-(3-chloro-2-hydroxypropyl)-N,N,N-trimethylammonium chloride 

Relevant academic research and scientific papers

Short and Practical Syntheses of (R)-(-)-Carnitine and (R)-(-)-γ-Amino-β-hydroxybutyric Acid (GABOB)

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.

Asymmetric synthesis of l-carnitine from (R)-3-chloro-1,2-propanediol

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.

Preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as starting material

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.

Synthesis method of L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine

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.

Novel method for preparing L-carnitine

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.

Preparation method of levocarnitine

The invention provides a preparation method of levocarnitine. The preparation method comprises the following steps: taking epoxy chloropropane as a starting material, then carrying out amination, cyaniding and carrying out ester exchange under the action of lipase CALB to obtain corresponding chiral ester, then carrying out alkaline hydrolysis and acidification, and then removing chlorine ions under the action of strongly alkaline resin, so that the levocarnitine finished product is obtained. In the invention, acid resin is used in an ester exchange process, and recemization can be realized, so that yield and optical purity of the levocarnitine are improved.

Practical and efficient utilisation of (R)-3-chloro-1,2-propanediol in synthesis of L-carnitine

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.

A PREPARATION METHOD OF HIGH-PURITY L-CARNITINE

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%.

PREPARATION METHOD OF HIGH-PURITY L-CARNITINE

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%.

PROCESS FOR PRODUCTION OF BETAINE

According to the present invention, by using 4-halogeno-3-hydroxybutanamide as a substrate in quaternary amination reaction with trialkylamine which is an important step in betaine (such as carnitine) preparation processes, it becomes possible to reduce the production of crotonic acid derivatives (the major by-product) greatly compared to conventional processes. Consequently, it becomes possible to prepare a betaine, such as carnitine, at a high yield. The present invention also relates to a process for preparing a betaine represented by formula (1) below, comprising a step of quaternary aminating an amide represented by formula (2) below: wherein A1, A2 and A3 individually represent a C1-C20 hydrocarbon group which may have a substituent(s); and X1 is a halogen atom.