Method for synthesizing metaraminol bitartrate

Abstract

The invention provides a process for synthesizing metaraminol bitartrate. The process comprises the following steps: taking carbobenzoxy-L-alanine as a raw material, carrying out a cyclization reaction, and carrying out a reaction with a Grignard reagent so as to prepare an intermediate (4S)-N-carbobenzoxy-5-(3-(benzyloxy)phenyl)-5-hydroxy-4-methyloxazolane; carrying out a hydrolytic ring-opening reaction on the intermediate, and producing (2S)-2-(carbobenzoxy)amino-1-(3-benzyloxyphenyl)-1-acetone; carrying out a reduction reaction on the (2S)-2-(carbobenzoxy)amino-1-(3-benzyloxyphenyl)-1-acetone so as to obtain (1R,2S)-2-(carbobenzoxy)amino-1-(3-benzyloxyphenyl)-1-propanol; performing deprotection on the (1R,2S)-2-(carbobenzoxy)amino-1-(3-benzyloxyphenyl)-1-propanol so as to obtain metaraminol; finally, performing salt formation on metaraminol and L-tartaric acid, thereby obtaining the metaraminol bitartrate. According to the method disclosed by the invention, usage of an expensive catalyst and chiral resolution can be avoided, and the cost is greatly reduced; by utilizing chemical synthesis, industrial production of optical pure metaraminol bitartrate becomes possible.

Description

technical field [0001] The invention relates to a synthesis method of metaraminol bitartrate, which belongs to the technical field of pharmaceutical synthesis. Background technique [0002] Metaraminol bitartrate mainly acts on α-receptors and has a weaker effect on β1-receptors; part of the effect is by promoting the release of norepinephrine from sympathetic nerve endings. It is suitable for early treatment of shock and prevention of acute hypotension during neuraxial block anesthesia. It is used for adjuvant symptomatic treatment of hypotension due to bleeding, drug allergy, surgical complications, traumatic brain injury or brain tumor combined with shock, and can also be used for the treatment of hypotension caused by cardiogenic shock or sepsis. [0003] At present, the method for industrially producing metaraminol bitartrate is biological fermentation, which has the disadvantages of small output and relatively high cost. Some researchers also try to use chiral cataly...

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Problems solved by technology

[0003] At present, the method of industrially producing metaraminol bitartrate is biological fermentation, and its disadvantage is that the output is small and the cost is relatively high

There are also some researchers who try to use the reduction method of chiral catalytic system, but the disadvantage is that the chiral catalyst and ligand are very expensive, and the production cost is very high. Currently, it is only used in the laboratory test stage

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