Method of preparing disodium methyl nitrozole phosphate

Abstract

The method for preparing metronidazole disodium phosphate salt includes two steps: first step uses metroindazole as raw material, and makes it react with catalyst and phosphoric acid esterification agent to obtain metronidazole chlorophosphoric acid intermediate, makes the intermediate undergo the process of hydrolysis to obtain metronidazole phosphate; and the second step uses water and metal alcohol as reaction medium, and makes the metroindazole phosphate react with carbonate or sodium hydroxide to obtain the aqueous or alcoholic solution of metronidazole disodium phosphate salt, then uses active carbon to decolour said solution, then makes the decoloured solution undergo the processes of concentration and precipitation with organic solvent.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and relates to a preparation method of metronidazole phosphate disodium salt. technical background [0002] Metronidazole is the basic and first-choice drug widely used in clinical anti-anaerobic infection, and it can also be used as a synergist in radiotherapy for malignant tumors. Because metronidazole has poor water solubility, when it is used for intravenous infusion, in order to ensure that it can be fully dissolved, a large volume of solvent is usually required during the preparation process. Due to the large amount of liquid medicine, the intravenous infusion time is longer, causing unnecessary pain to the patient; at the same time, because of incompatibility, metronidazole often must be used alone, and the large-capacity liquid medicine is also used for other drugs that require intravenous infusion. Application limits. In addition, in the process of production, storage and transportatio...

AI Technical Summary

Problems solved by technology

The above-mentioned U.S. Patent No. 4,531,004 prepares the method shortcoming of metronidazole phosphate ester and is: (1) operation is complicated, needs protection with nitrogen

(2) The reaction conditions are harsh and need to be reacted at -20°C-30°C

(3) The amount of solvent is large, the amount of tetrahydrofuran is large, the price is relatively expensive, and the cost is high (metronidazole: tetrahydrofuran = 1: 56.43mol)

The shortcoming of above-mentioned metronidazole phosphate disodium salt is: (1) operation is complicated, and 2-cyano ethyl phosphate needs first to refine through cation exchange resin

(2) Large amount of solvent

[0005] And about the method for preparing metronidazole phosphate disodium salt, U.S. Patent 4160827 is to react with NaOH aqueous solution and metronidazole phosphate, then neutralize with hydrochloric acid, evaporate the water under reduced pressure at 45 ℃, and then use methanol to extract the formed formazan Nitazole phosphate disodium salt is obtained by further refining. Since the aqueous solution of metronidazole phosphate disodium salt is at a temperature higher than 40°C, the color will change if the duration is too long, the refining is inconvenient, and the operation is complicated, so it is not suitable for industrial production.