A kind of synthetic method of cefcapene hydrochloride

Abstract

The invention discloses a cefcapene pivoxil hydrochloride synthesis method, and belongs to the technical field of synthesis of cephalosporin medicines. The cefcapene pivoxil hydrochloride synthesis method comprises the following steps: (1) using BCN as a starting material, reacting with an inorganic acid aqueous solution in a solvent to obtain a dissolved clarified solution, standing, layering, abandoning a water layer, collecting an organic layer comprising a compound I, and drying; (2) adding a formic acid and a concentrated hydrochloric acid, reacting at the temperature of 0-5 DEG C, washing with water after finishing reacting, layering, and collecting an organic layer comprising a compound II; (3) adding a sodium bicarbonate aqueous solution and iodomethyl pivalate, maintaining the pHvalue to 5-6, layering after finishing reacting, collecting the organic layer, adding ethanol, washing with water, layering, additionally adding the ethanol in the organic layer, regulating the pH value to 7-8 by using an inorganic base, layering, and collecting an organic layer comprising a compound III; and (4) conducting vacuum concentration until no liquid drop is distilled, adding a solvent,adding a diluted hydrochloric acid, regulating the crystallization, cooling, growing the crystal, conducting suction filtration, and drying to obtain cefcapene pivoxil hydrochloride. The process of the method is simple, the reaction condition is mild, the method is environmentally friendly, the yield is high, the purity is high, and the method is easy for industrial production.

Description

technical field

[0001] The invention belongs to the technical field of synthesis of cephalosporins, in particular to a synthesis method of cefcapene hydrochloride. Background technique

[0002] Cefcapene Proxil Hydrochloride, chemical name: (6R,7R)-3-(((carbamoyl)oxy)methyl)-7-(((2Z)-2-(2-amino-4-thiazolyl) -1-oxo-2-pentene)amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-ene-2-carboxylic acid-2,2-di Methyl pivaloyloxymethyl ester hydrochloride monohydrate, its structural formula is:

[0003]

[0004] Cefcapene pivoxil hydrochloride is a broad-spectrum cephalosporin antibiotic. It was first developed by Shionogi Pharmaceutical Co., Ltd. in Japan. It was listed in Japan for the first time in 1997 under the trade name Flomox. Spectrum antibiotics.

[0005] Since multiple parts of the β-lactam ring in the structure of cefcapene pivoxil hydrochloride are prone to degradation reactions, the stability of cefcapene pivoxil hydrochloride is poor. The impurities in the finished...

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