Preparation method of flupentixol dihydrochloride

Abstract

The invention provides a preparation method of flupentixol dihydrochloride, which comprises the following steps: reacting and dehydrating 10-hydroxy-10-(3-dimethylaminopropyl)-2-trifluoromethyl thioxanthene and sulfoxide chloride or acetic anhydride to prepare high-content Z-type 10-[3-(EZ)-dimethylaminopropyl]-2-trifluoromethyl thioxanthene, reacting with N-hydroxyethyl piperazidine to prepare flupentixol base, and finally, introducing sufficient hydrochloric acid gas into the flupentixol base to prepare the high-content Z-type flupentixol dihydrochloride. The method has the advantages of fewer steps, high yield and high product purity, is simple to operate, and does not use any extremely toxic substance to pollute the environment. The Z-type flupentixol dihydrochloride content in the flupentixol dihydrochloride prepared by the method is 42-52%, and conforms to the quality standard specification for flupentixol dihydrochloride in European Pharmacopoeia.

Description

technical field

[0001] The invention relates to a preparation method of flupenthixol hydrochloride, in particular to a preparation method of flupenthixol hydrochloride with a medicinal Z-type content of 42% to 52%. Background technique

[0002] Flupenthixol hydrochloride is the dihydrochloride of flupenthixol, and its combination compound preparation with melitracen hydrochloride (trade name: Deanxit) is used to treat depression, anxiety and severe tension. The structural formula of flupenthixol is as follows:

[0003]

[0004] The quality standard of flupenthixol hydrochloride recorded in the European Pharmacopoeia stipulates that the content of the Z-isomer should be in the range of 42.0% to 52.0%. Acceptance is a very difficult thing. There are mainly two kinds of existing preparation technologies, one is to separate and purify type Z and type E, and mix the two isomers in a certain proportion to prepare flupentixol hydrochloride medicinal product; the other is to co...

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