Fosfomycin disodium preparation method

Abstract

The invention discloses a fosfomycin disodium preparation method. According to the method, based on the high solubility of fosfomycin monosodium in industrial ethanol and the almost insolubility of fosfomycin disodium in industrial ethanol, industrial ethanol is used as the single solvent, and sodium hydroxide reacts with L-cis-1,2-epoxypropylphosphonic acid-D-alpha-phenylethylamine in industrialethanol, wherein fosfomycin disodium can be formed to cause turbidity when the added sodium hydroxide is excessive so as to accurately control the adding amount of sodium hydroxide based on the condition, such that the adding of sodium hydroxide is stopped before the formation of fosfomycin disodium; then active carbon is added to decolorize, and impurities are removed to obtain the mixed solutionof impurity-free fosfomycin monosodium and industrial ethanol; and a sodium hydroxide ethanol solution is added to the mixed solution of impurity-free fosfomycin monosodium and industrial ethanol, and a reaction is performed to obtain the final product fosfomycin disodium, wherein no impurity exist, and the filtrates in the steps c and d can be continuously and repeatedly used after centrifugal filtration, such that the consumption of the solvent ethanol is substantially reduced, and the production cost is reduced.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of fosfomycin sodium. Background technique [0002] As a new type of antibiotic drug, fosfomycin sodium usually exists in the form of sodium salt, calcium salt and ammonium salt, among which sodium salt is used for intravenous drip or injection, and its antibacterial spectrum is wider than that of penicillins and cephalosporins. Widely used in Japan and Europe. [0003] There are many preparation methods for fosfomycin sodium, such as sodium methoxide method, sodium hydroxide solution method and spray drying method. The sodium methoxide method is to dissolve with methanol and use acetone to crystallize. This method uses a mixed solvent, which makes solvent separation difficult and cannot be recycled. The loss of water ethanol is relatively large. Spray-drying is to directly obtain fosfomycin sodium salt by spraying the sodium salt aqueous solution with spr...

AI Technical Summary

Problems solved by technology

The sodium methoxide method is to dissolve with methanol and use acetone for crystallization. This method uses a mixed solvent, which makes solvent separation difficult and cannot be recycled. The sodium hydroxide aqueous solution method needs to use a large amount of dehydrated alcohol solvent for crystallization, resulting in no The loss of water and ethanol is large

Spray drying is to directly obtain fosfomycin sodium salt from sodium salt solution with spray drying equipment. Although the amount of solvent used in this method is small, the spray drying equipment is huge

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