# US 4,400,503 A · Purification of syn-7-[[(2-amino-4-thiazolyl)(methoxyimino) acetyl]amino]-3-methyl-3-cephem-4-carboxylic acid

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- Number: US 4,400,503 A
- Document ID: US4400503A
- Status: Granted
- Kind: A
- Application number: 06/316,615
- Filed: 1981-10-30
- Granted: 1983-08-23
- Earliest claimed: 1981-10-30
- Assignees: Eli Lilly and Company
- Inventors: Kuo S. Yang
- Web page: https://patentgrep.com/patent/US4400503A

## CPC

- C07D 501/22: with radicals containing only hydrogen and carbon atoms, attached in position 3
- A61P 31/04: Antibacterial agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Crystalline cephalosporin hydrochloride salt represented by the formula ##STR1## wherein the oxime is in the syn configuration, is a useful pharmaceutical form of, and tool for purification of, the corresponding antibiotic free base; processes for its preparation are provided.

## Claims

### Claim 1

The process for purifying the compound of formula 2: ##STR4## wherein the oxime is in the syn configuration which comprises preparing the crystalline hydrochloride salt of the formula 2 compound by (a) adding this compound to a solvent selected from water or a polar organic solvent to form a solution or slurry; (b) adding hydrochloric acid to give a solution which has a pH of between about 1.5 and 3.5; (c) maintaining the solution until crystallization occurs; (d) separating the crystalline salt; (e) dissolving the crystalline salt in an aqueous bicarbonate solution with the pH maintained between about 6 and about 7; (f) filtering the solution to separate solid impurities; and (g) adding hydrochloric acid to the filtered solution until free base of formula 2 precipitates.

### Claim 2 (depends on 1)

The process of claim 1 wherein the solvent in step (a) is formamide.

### Claim 3 (depends on 1)

The process of claim 1 wherein the solvent in step (a) is ethanol.

### Claim 4 (depends on 3)

The process of claim 3 wherein the temperature of step (a) is between about 30.degree. to about 45.degree. C., the amount of hydrochloric acid in step (b) is from about 1 to about 2 equivalents, and the solution in step (c) is stirred at a temperature of between about 30.degree. to about 45.degree. C. until the compound is in solution and then is cooled to room temperature or below until crystallization occurs.