Ethambutol hydrochloride synthesis method

Abstract

The application of the invention discloses an ethambutol hydrochloride preparation process. The ethambutol hydrochloride preparation process comprises the following steps: 1) mixing S-(+)-2-amino-1-butanol and 1,2-dichloroethane, reacting to form a reaction discharge material; 2) separating S-(+)-2-amino-1-butanol from the reaction discharge material in a separating system, returning to a reactor;3) adding HCl into the separation system; 4) crystalizing to obtain a first mother solution and precipitated ethambutol hydrochloride; 5) concentrating the first mother solution at the normal pressure to recycle alcohol, crystalizing to obtain a second mother solution and the ethambutol hydrochloride, enabling the ethambutol hydrochloride to return to the separation system; 6) adding an alkali into the second mother solution to regulate the pH value, separating the alcohol and the S-(+)-2-amino-1-butanol not completely separated in the step 2), and dehydrating the separated S-(+)-2-amino-1-butanol in the step, and enabling the S-(+)-2-amino-1-butanol to return to the reactor.

Description

technical field [0001] The application relates to a method for synthesizing ethambutol hydrochloride. Background technique [0002] Ethambutol hydrochloride is widely used in combination with other anti-tuberculosis drugs to treat tuberculosis caused by Mycobacterium tuberculosis, and can also be used in the treatment of tuberculous meningitis and atypical mycobacterial infection. The drug accounts for more than 13% of the anti-TB drug market share. [0003] Ethambutol hydrochloride (English name is Ethambutol Hydrochloride), its chemical name is [2R,2[S-(R * , R * )-R](+)-2,2`-(1,2-Ethylenediimino)-bis-1-butanol dihydrochloride, the molecular formula is C 10 h 24 N 2 o 2 HCl, the molecular weight is 277.23, the CAS number is 1070-11-7, and its structural formula is: [0004] [0005] The currently reported synthesis methods include 1,2-epoxy-3-butene, (S)-2-aminobutyric acid ethyl ester, S-(+)-2-amino-1-butanol, etc. as starting materials synthesis process. [0...

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Problems solved by technology

[0006] And take 1,2-epoxy-3-butene as the method for starting raw material to prepare ethambutol hydrochloride has following shortcoming: because 1,2-epoxy-3-butene is gas, increased equipment complexity, It is difficult to control the amount of feed, and there are too many synthesis processes

[0007] With (S)-2-aminobutyric acid ethyl ester as the shortcoming of the method for starting raw material: raw material is difficult to obtain, and price is more expensive, and production cost is too high

[0008] At present, the most widely used method is to directly condense S-(+)-2-amino-1-butanol and 1,2-dichloroethane to prepare ethambutol. After the condensation is completed, it needs to be neutralized with NaOH The yield of HCl produced is low, and NaOH is more corrosive to equipment

[0009] However, the method of protecting the amino group first and then condensing also has the following disadvantages: too many types of raw materials, relatively complicated operations, many impurities in the product, and difficult to scale application

Therefore, this method takes a long time for the equipment and consumes a lot of energy, which limits the production progress of large-scale production rolling feeding

Moreover, HCl gas is not easy to transport. If it is self-made, it will produce a large amount of strong acid waste liquid, which is difficult to handle.

Therefore, this method limits the application of large-scale production

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