Synthesis method of metaraminol bitartrate

Abstract

The invention discloses a synthesis method of metaraminol bitartrate, and in particular provides a method for synthesizing metaraminol bitartrate by using a chiral catalysis method. The synthesis method comprises the steps: catalyzing a chiral addition reaction of hydroxybenzaldehyde and nitroethane by using a chiral catalyst system consisting of cinchona alkaloid, copper acetate hydrate and less imidazole to obtain an addition product with a dominant required spatial configuration, and then reducing nitro by using hydrogen in the presence of Pd-C to obtain amine to obtain aramine, and salifying the aramine with L(+)-tartaric acid to obtain a final product metaraminol bitartrate. According to the synthesis method, an enzyme catalyst is prevented from being used, a raw material of the synthesis reaction is easily available, the chiral catalyst is easily purchased or prepared self, the synthesis steps are relatively less, the chiral control efficiency is higher, the enantioselectivity is high, the yield is good, the reaction operation is easily controlled, and is safe and reliable, and the foundation is laid for the later industrialized amplification production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a synthesis method of metaraminol bitartrate. Background technique [0002] Metaraminol bitartrate, Chinese alias: Alamin, English alias: Metaraminal bitartrate, CAS number: 33402-03-8, molecular formula C 9 h 13 NO 2 ·C 4 h 6 o 6 , molecular weight 317.29) is the bitartrate of metaraminolamine. [0003] At present, the common synthetic methods of metaraminol are as follows: [0004] 1. Use m-hydroxypropiophenone as raw material to obtain the target product after hydroxyl protection, nitrosation, Raney nickel hydrogenation reductive amination, and then deprotection. The reaction formula is shown in formula 1: [0005] [0006] Formula 1 [0007] 2. Take m-hydroxybenzaldehyde as a raw material to obtain 1-acetyl-m-hydroxybenzyl alcohol through enzyme catalysis in the presence of D-glucose, and obtain the target product by reduction and deprotection in the presence of ammon...

AI Technical Summary

Problems solved by technology

[0013] The first synthetic method has 4-step reactions, the starting material m-hydroxypropiophenone needs to be custom synthesized, and the second reduction reaction involves chiral reduction, which limits industrial application

[0014] The second synthesis method actually has 3 steps of reaction, which requires the use of enzymes as catalysts. There are many key technologies involved in the acquisition, activity, and catalytic ability of enzymes, which are technically difficult; the second reduction reaction still faces the problem of chiral reduction. question

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