A kind of preparation method of erythrostructure methoxamine hydrochloride

Abstract

A disclosed preparation method for erythro-structure methoxamine hydrochloride comprises the following steps: (1) dissolving an initial raw material 2,5-dimethylpropiophenone in an organic solvent, under the condition of introducing dry hydrogen chloride gas, dropwise adding a 1-butyl nitrite solution to perform an oximation reaction, so as to obtain an intermediate I; (2) under the acidic condition, taking a methanol solution as a solvent, take palladium on activated carbon as a catalyst, employing hydrogen to reduce the oximido group in the intermediate I, so as to obtain an intermediate II; and (3) performing hydrogenation reduction reaction on the intermediate II to obtain the erythro-structure methoxamine hydrochloride. The method provided by the invention is simple in operation, economic, environment-friendly, mild in reaction conditions, excellent in product quality and high in yield, and can help to obtain the single erythro-structure methoxamine hydrochloride.

Description

technical field [0001] The invention relates to the field of chemical medicines, in particular to a preparation method of methoxamine hydrochloride with an erythro-structure. Background technique [0002] The chemical name of Methoxamine Hydrochloride is: α-(1-aminoethyl)-2,5-dimethoxybenzyl alcohol hydrochloride, which is an α-receptor agonist with obvious vasoconstriction It can increase both systolic and diastolic blood pressure by increasing peripheral resistance, so that it has no exciting effect on the heart. It is suitable for hypotension caused by hemorrhage, trauma, and surgery, as well as the prevention of hypotension and supraventricular paroxysmal tachycardia before spinal anesthesia; it can also be used for postoperative circulatory failure and peripheral circulatory failure. hypotensive shock. [0003] According to Richard Baltzly (J.Am.Chem.Soc., 1942, 64(12), p3040, J.Med.Chem., 1968, 11(4), pp833-844) reported that the main pharmacological active substance...

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Problems solved by technology

[0009] AlanE (J.Am.Chem.Soc., 1946, 68(4), pp591–595) et al. used route a) to prepare methoxamine hydrochloride, but bromine was used in the preparation process, and there was a large amount of hydrogen bromide Gas is produced, and bromine is poisonous and volatile, which is likely to have adverse effects on the human body and the environment

[0010] U.S. Patent US5962737 and MarkA. (J.Chem., 1990,43,79-86) once reported adopting route b) to prepare methoxamine hydrochloride, but what this route generates is threo formula, erythro formula mixture, will prepare independent erythro The formula structure also needs column chromatography to separate intermediates or carry out structural conversion by chemical methods. The operation is relatively cumbersome, and the yield is low. The product quality needs further investigation, which is not conducive to industrial production.

[0011] U.S. Patent No. 7,414,153 once reported that route c) was used to prepare methoxamine hydrochloride, but its raw materials are not easy to obtain, and a small amount of threo isomers are produced during reduction.

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