Preparation method of L-carnitine compound

Abstract

The invention discloses a preparation method of a levocarnitine compound, and the preparation method is applied to the technical field of pharmaceutical chemical synthesis. The preparation method comprises the following steps that (1), 4-chloroacetoacetic acid ethyl ester serves as the initial raw material, under the condition that a solvent exists, an asymmetric catalyst phosphine ligand ruthenium complex is applied for hydrogenation reduction, and (R)-4-chlorine-3-hydroxybutyrate ethyl ester is obtained by vacuum concentration and high vacuum distillation; (2), a trimethylamine squeous solution and the (R)-4-chlorine-3-hydroxybutyrate ethyl ester are added dropwise and slowly in the solvent comprising inorganic base, the dropping speed is controlled, low temperature reaction is carried out, then indoor temperature reaction is carried out, the pH of the mixture is adjusted to be 6 through concentrated hydrochloric acid after reaction is finished, and the levocarnitine compound is obtained by resin column purification. According to the method, the asymmetric catalytic reaction is applied, the two-step reaction that an optical active intermediate with high optical purity and high yield can be obtained and the optical active intermediate is converted to be the levocarnitine compound is the one-pot reaction, the water serves as the reaction solvent, the inorganic base is used for catalysis, the unique process of indoor temperature reaction is adopted, the product quality is good, the purity is high, the yield can reach up to 80%, the reaction steps of the preparation method are short, operation is easy, pollution to environment is small, and green resources are protected.

Description

technical field [0001] The invention relates to a preparation method of a levocarnitine compound in the technical field of pharmaceutical chemical synthesis. Background technique [0002] Levocarnitine, also known as L-carnitine, chemical name: (R)-3-carboxy-2-hydroxy-N,N,N-trimethyl-1-propylammonium hydroxide inner salt, molecular formula: C 7 h 15 NO 3 , molecular weight: 161.20. L-carnitine is necessary for human metabolism, is an important part of food, and is considered a "vitamin-like" nutrient. It is an amino acid that widely exists in the human body. Its most prominent physiological function is to transport long-chain fatty acids in the body into the mitochondria for β-oxidation to become the energy necessary for the human body. Human muscle cells and muscle cells rely on this fat The function of oxidation is to obtain energy. There are two sources of L-carnitine in the human body. One is dietary intake, which is the most abundant in meat and dairy products, and...

AI Technical Summary

Problems solved by technology

The {[Ru(p-cymene)I(+)TMBTP]I} chiral catalyst used in this patent has no industrial production, the preparation process is complicated, and the cost is extremely high, so it cannot be used in industrial production; 45% trimethylamine aqueous solution is used for amination , Preparation of levocarnitine by hydrolysis, there are problems such as high temperature and long reaction time, resulting in many side reactions, many impurities, and low yield

The existing production technology of levocarnitine varieties is backward, the separation method is seriously wasteful, the product quality is not high, the pollutants are difficult to deal with, and highly toxic sodium cyanide is used, which is dangerous, unfriendly to the environment, and large investment in equipment, etc.

Images