Preparation method of cefcapene pivoxil hydrochloride

Abstract

The invention discloses a one-step preparation method of an antibiotic drug cefcapene pivoxil hydrochloride monohydrate. The preparation method comprises the following steps: adding hydrochloric acidand trifluoroacetic acid into an organic solvent, stirring and cooling to 0 to -10 DEG C, adding Boc-based protected cefcapene pivoxil, continuing to keep the temperature and carrying out stirring, and after the reaction is finished, carrying out crystallizing, filtering and drying to obtain a cefcapene pivoxil hydrochloride monohydrate, wherein the molar ratio of hydrochloric acid to trifluoroacetic acid is 10: 1 to 5: 1. The preparation method of cefcapene pivoxil hydrochloride provided by the invention is high in yield, low in cost, convenient in treatment, good in stability, mild in reaction condition, environment-friendly and suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of cefcapene pivoxil hydrochloride, in particular to a preparation method for removing the Boc protecting group in the production process of cefcapene pixil hydrochloride. Background technique [0002] The chemical name of cefcapene pivoxil hydrochloride is 7-[2-(2-amino-1,3-thiazol-4-yl)pent-3-enamido]-3-(carbamoyloxymethyl)-8 -Oxo-5-thio-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2,2-dimethylpropionyloxymethyl ester hydrochloride monohydrate. [0003] Cefcapene pivoxil hydrochloride is the third generation of oral cephalosporin antibiotics. Pharmacological studies have shown that the MIC80 against MSSA of aerobic G+ bacteria is 3.13 μg / ml, which is the same as that of cefotiam and cefaclor, and the MIC80 against Streptococcus pneumoniae ≤0.1μg / ml, superior to cefaclor, comparable to cefditoren, highly active against penicillin-resistant (including moderately resistant) Streptococcus pneumoniae, with ...

AI Technical Summary

Problems solved by technology

[0004] Most of the existing processes use N-Boc-protected cefcapene proxetil as an intermediate, use trifluoroacetic acid to remove the protecting group, and then form a salt, which has difficulties in handling and unstable materials, and is not suitable for industrial scale-up production

CN102796117 discloses that the cefcapene pivoxil hydrochloride monohydrate is obtained by removing the Boc protection of N-Boc-protected cefcapene pivoxil through acid, and then salting to obtain cefcapene pixil hydrochloride monohydrate. Although this method is a one-pot method, it is slightly improved compared with the conventional method, but There is little difference in essence, the operation is cumbersome, and the yield is not high