Process for preparing L-ofloxacin and ofloxacin

Abstract

The invention relates to a process for preparing L-ofloxacin and ofloxacin which consists of, charging solution into 2-(2,3,4,5-tetrafluorobenzoyl-3-ethoxy-ethyl acrylate crude product, freezing, dropping L-amino propanol or DL-amino propanol, thermal insulating till the completion of conversion, alkalizing, reacting at the temperature of 50-90 deg. C, charging N-methyl piperazine into mother liquor, stirring for reaction 1-3 hours at 55-95 deg. C, decompressing and reclaiming N-methyl piperazidine, thermal insulating, plunging reaction liquor into water, agitating, cooling down and filtering, charging water and acid into filtrate, stirring, inversing flow till the completion of hydrolysis, adjusting the pH=7.0 with alkali liquor, extracting by adding in solvent extraction reagent, and concentrating the extract layer.

Description

technical field [0001] The invention belongs to the field of chemistry, in particular to a preparation method of levofloxacin and ofloxacin. Background technique [0002] Fluoroquinolones have achieved great success in clinical anti-infection treatment due to their high-efficiency, broad-spectrum, and low-toxic antibacterial properties. Ofloxacin and levofloxacin developed by Japan's Daiichi Pharmaceutical Company are excellent varieties among them . Levofloxacin, English name: Leovfloxacin, molecular formula: C 18 h 20 FN 3 o 4 1 / 2H 2 O, the structural formula is as follows: [0003] [0004] Ofloxacin, English name: Floxacin, molecular formula: C 18 h 20 FN 3 o 4 , the structural formula is as follows: [0005] [0006] The synthesis of levofloxacin mainly contains the following three methods: [0007] 1. Resolution method: including high-pressure liquid phase resolution EP206283 (1986) and enzyme resolution (K, Sakano, Agina Biol.chem.: 1987, 51, 1265). ...

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Problems solved by technology

[0014] In the above-mentioned two synthetic routes, the route of synthesizing the final products (levofloxacin and ofloxacin) from compound (V) first forms two rings simultaneously, then hydrolyzes, and finally N at the 10-position -Methylpiperazinyl, there are the following disadvantages in this section of the synthetic route: 1) due to the different solvents in each step of the reaction (generally adopting N,N-dimethylformamide or N,N-dimethylsulfoxide and water), It cannot be operated continuously in the same reactor, and it needs to be operated in four steps. The amount of solid transfer is large, there is a lot of dust, and it is difficult to ensure a satisfactory recovery rate of the solvent; 2) In order to meet the simultaneous loading of two rings, the reaction is not easy to carry out , make the temperature during preparation be 120-150 ℃, the time is 4-5hr, the reaction time under high temperature is long, side reaction easily takes place, and product quality and outward appearance can be affected; 3) need a large amount of glacial acetic acid, and production cost is big, The hydrolysis reaction time is 5-6 hours long, it is difficult to dissolve, it is not easy to hydrolyze completely, it is difficult to separate after the reaction, and it has a great impact on the environment

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