Preparing method of (2R,4R)-4-methylpiperidine-2-ethyl formate compound

Abstract

The invention relates to a preparing method of a (2R,4R)-4-methylpiperidine-2-ethyl formate compound. The method comprises the following steps of 1, regarding 4-methyl-2-cyanopiperidine as an initialraw material to be subjected to a hydrolysis reaction through hydrochloric acid to obtain 4-methyl-2-piperidinecarboxylicacid hydrochloride; 2, using ethyl alcohol to esterify 4-methyl-2-piperidinecarboxylicacid hydrochloride to obtain 4-methyl-2-ethyl nipecotate hydrochloride; 3, adding a mixed solvent of methyl tertiary butyl ether and ethyl alcohol, reacting the mixed liquid for pulping, filtering to remove cis-form 4-methyl-2-ethyl nipecotate hydrochloride solid, and collecting mother liquor to obtain anti-form 4-methyl-2-ethyl nipecotate hydrochloride; 4, using L-tartaric acid to split anti-form 4-methyl-2-ethyl nipecotate to obtain the target product (2R,4R)-4-methylpiperidine-2-ethyl formate.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and more particularly relates to a preparation method of (2R,4R)-4-methylpiperidine-2-ethyl carboxylate. Background technique [0002] Argatroban (Argatroban), the chemical structure is as follows: [0003] [0004] Argatroban Alias: Argodropan, Argotoban, is a white powder chemical. Its chemical name is: (2R,4R)-4-methyl-1-[N-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]-L -Arginyl]-2-piperidinecarboxylic acid. [0005] Argatroban is an anticoagulant drug, which was first listed in Japan in 1990, approved by the US FDA in 2000, and launched in my country in 2002. Argatroban can be used as a treatment and prevention of thrombosis and platelet aggregation inhibitors, treatment of chronic arterial blockage and treatment of cerebral thrombosis and other drugs. The structure of argatroban contains an important trans-piperidine acid structural unit: (2R,4R)-4-methylpiperidin...

AI Technical Summary

Problems solved by technology

[0020] In summary, the method for the synthesis of argatroban intermediate (2R, 4R)-4-methylpiperidine-2-ethyl carboxylate reported in the above bibliographical data has obvious deficiencies, or the catalyst is expensive and the cost is too high. High, or the route is long, contains dangerous reactions such as hydrogenation, there are safety problems, or the operation is complicated when removing isomers, which is not conducive to large-scale production, etc.

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