A kind of preparation method of methyl 4-acetamidomethylcyclohexylcarboxylate

Abstract

The invention relates to a preparation method of methyl 4-acetamidomethylcyclohexylcarboxylate. It first adds methyl p-cyanobenzoate into the reaction kettle, uses acetic anhydride as solvent, adds metal catalyst I and co-catalyst II, heats up and stirs under hydrogen condition for 6-10 hours, then filters and distills to obtain p-acetamide methyl benzoate; then add the obtained methyl p-acetamidomethyl benzoate into the reaction kettle, add solvent V, metal catalyst Ⅲ and cocatalyst Ⅳ, heat up and stir under hydrogen condition to complete the reaction, then filter and distill The solvent is recovered to obtain methyl 4-acetamidomethylcyclohexylcarboxylate. The synthesis process of the present invention using methyl p-cyanobenzoate as the starting material to prepare methyl 4-acetamidomethylcyclohexylcarboxylate has the advantages of easy access to raw materials, low cost, high yield, simple operation, and is suitable for industrialization Production and other advantages, the product can be further used to prepare trans-4-aminomethyl cyclohexanecarboxylic acid, the application potential is great.

Description

technical field [0001] The invention relates to a preparation method of methyl 4-acetamidomethylcyclohexylcarboxylate, a key intermediate of trans-4-aminomethylcyclohexylcarboxylate. Background technique [0002] Trans-4-aminomethylcyclohexanecarboxylic acid, also known as tranexamic acid and tranexamic acid, is a synthetic amino acid with hemostatic and anti-inflammatory pharmacological effects. It belongs to fibrinolysis inhibitors and is widely used clinically. Various bleeding disorders and abnormal bleeding during surgery in the fields of surgery, internal medicine, urology and obstetrics and gynecology. [0003] At present, there are many chemical methods for synthesizing trans-4-aminomethylcyclohexanecarboxylic acid, and using p-cyanobenzoic acid as the main intermediate or starting material is an important class of methods, mainly including the following: 1 ) using p-methylbenzonitrile as the starting material, oxidized to p-cyanobenzoic acid, and then using Raney n...

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Problems solved by technology

[0003] At present, there are many chemical methods for synthesizing trans-4-aminomethylcyclohexanecarboxylic acid, with p-cyanobenzoic acid as the main intermediate or starting material One of the more important methods mainly includes the following: 1) using p-tolunitrile as the starting raw material to obtain p-cyanobenzoic acid through oxidation, and then using Raney nickel and metal platinum to catalyze the hydrogenation of cyano and Benzene ring, finally recrystallized to obtain trans-4-aminomethylcyclohexylcarboxylic acid (Satyavathi, K.Orient.J.Chem., 2009,25(4):987-992.); 2) Using p-cyanobenzoic acid as the starting material, hydrogenation of the cyano group by Raney nickel catalyzes p-aminomethylbenzoic acid, that is, hemostatic aromatic acid (WO2006053882A2), and hemostatic aromatic acid can be hydrogenated through the benzene ring, iso structure to prepare trans-4-aminomethylcyclohexanecarboxylic acid, the problem is that the catalysts used are all expensive, such as the Pt-M / C catalyst (M=Ru, La, Ce, Co, Ni) used in CN102276490A; CN100336799C uses PtO2 catalyst; or uses LiBH4 as a reducing agent to reduce cyano groups (JP63255252A); 3) also uses p-cyanobenzoic acid as a starting material , about 73% trans-4-aminomethylcyclohexanecarboxylic acid was obtained by catalytic hydrogenation of Pd-Al2O3 and Ru-C under barium hydroxide (JP57188547A)

But it also requires the use of expensive platinum-based metal catalysts

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