Patent EA-000277-B1 (EA)
Title: Clavulanic acid extraction process
Inventor: RUDDICK SIMON
IPC: C07D499/18
Filed: 1996-01-17
Abstract: 1. An aqueous extraction process in which a stream of a substantially water imiscible organic solvent containing a water-soluble organic solute which is a beta-lactam antibiotic, such as a penicillin or cephalosporin, or clavulanic acid, as the free acid or a labile derivative or a salt thereof, is contacted at speed with a stream of an aqueous medium in a first mixing region, which is a region of high turbulence and/or shear stress, where the volume ratio of aqueous medium and organic solvent phase is in the range 1:200 to 1:50, so that a substantial proportion of the solute passes from the organic solvent into the aqueous medium in the first mixing region, then the organic solvent and aqueous phases are physically separated during a separation step provided that if the solute is an amine salt of clavulanic acid which is formed in situ in the first mixing region then the said amine salt is formed by reaction between clavulanic acid or a labile derivative thereof and an amine. 2. A process according to Claim 1, comprising further processing step in which the clavulanic acid salt thereof or water-soluble derivative thereof is isolated from the aqueous solution. 3. A process according to Claim 1 or 2 characterised in that the solute is in the form of a salt of a metal ion or of an organic base. 4. A process according to Claim 3 characterised in that the amine is selected from tertiary butylamine, ammonia, phenylethylamine, t-amylamine, t-ocrylamine, 1-hydroxy-2-methyl-2-propylamine, cyclopentylamine, cycloheptylamine, 1-adamantanamine, N-ethylpiperidine, N'N'-diisopropylethylenediamine and N N-dimethyl-cyclohexylamine. 5. A process according to Claim 1 or 2 characterised in that the organic solvent phase output from the separation step of the process, containing residual clavulanic acid in solution subjected in a two or more stage process for a second and optionally subsequent time to the said mixing and separation steps, to extract a further proportion of the solute. 6. A process according to Claim 1 or Claim 2 characterised in that part of the aqueous medium phase which is separated from the organic solvent in the separation stage is fed into the flow of aqueous medium entering the mixing region to produce an aqueous medium which is itself a dilute aqueous solution of the solute. 7. A process according to Claim 1 or Claim 2 characterised in that the separated organic solvent phase is subjected to a second separation stage at which a further proportion of the solute is extracted into the aqueous phase. 8. A process according to Claim 1 characterised in that the volume ratio of aqueous medium and organic solvent phase in the said mixing region is 1>=250. 9. A process according to Claim 6 characterised in that the separated aqueous medium phase from the further separation stage subsequent to the further mixing region is merged with the aqueous medium phase of similar concentrations from the separation stage subsequent to the first mixing region. 10. A process according to Claim 19 characterised in that the organic solvent separated subsequent to the further mixing region is circulated to extract a fresh charge of solute, or a precursor thereof, from an aqueous source of the solute or precursor. The Eurasian patent is valid in all Contracting States, except AM and MD.