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filingDate 1973-08-20-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 1974-03-12-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber IE-38106-L
titleOfInvention Preparation of penicillin sulfoxide
abstract 1388979 Preparing penicillin sulphoxides ELI LILLY & CO 21 Aug 1973 [12 Sept 1972] 39603/73 Heading C2C Penicillin sulphoxides are prepared from a penicillin-containing fermentation broth by filtering off the mycelium and adding a miscible organic liquid to the filtrate to precipitate non- penicillin impurities, oxidizing the penicillin in the solution with a per-acid oxidizing agent at -20 to 25‹ C., to produce the sulphoxide, lowering the pH of the resulting solution and adding water to induce crystallization of the sulphoxide, and separating the crystallized sulphoxide from the supernatant. The filtered broth containing the penicillin (e.g. phenoxymethyl- or benzyl-penicillin), is preferably concentrated to 200-400 mg. solid per ml. before adding the organic liquid, which is preferably acetone in ¢-3 volumes or may be methanol, ethanol, methyl ethyl ketone, acetonitrile, isopropanol, tert.-butanol or propionitrile. The precipitated impurities are usually filtered off, and if desired the organic liquid may then be removed. Oxidation is effected with an at least partially soluble oxidizing agent, in sufficient amount to convert all the penicillin content to the sulphoxide, e.g. 1-3 moles per mole of penicillin; the preferred agents are per-acetic acid, per-propionic acid, per-benzoic acid and per-succinic acid. The pH is then lowered to a crystallization point of the penicillin (i.e. about the iso-electric point), usually about pH 1À5-2À5, preferably with one of the following: methanesulphonic, p-toluenesulphonic, hydrochloric, sulphuric, o-phosphoric or nitric acid, and water is added to assist crystallization. The penicillin oxide crystallizes in pure form and is separated from the supernatant liquid.n[GB1388979A]
priorityDate 1972-09-12-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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