A PROCESS FOR THE PREPARATION OF AN ACEXAMIC ACID DERIVATIVE

Abstract: The invention relates to a process for the preparation of an acexamic acid derivative, namely the zinc salt of formula: [CH₃ - CONH - (CH₂)₅ COO]₂ Zn and is characterised in that the acexamic acid is react­ ed with zinc hydroxide in a polar solvent. It finds application in the manufacture of compounds having anti­ ulcer properties.

Description: The present invention relates to a process for the preparation of an acexamic acid derivative, namely the zinc salt of said acid. This salt, of formula [CH₃ - CONH - (CH₂)₅ - COO]₂ Zn has antiulcer properties. Background of the Invention. Zinc salts have been prepared up to now, among other methods, by using reactants such as basic zinc carbonate or zinc carbonate, which were reacted directly with the corresponding acid with the advantage, in compounds for pharmaceutical use, of avoiding the presence, as contaminants, of other anions (sulfates, chlorides, etc) derived from the prior preparation of the sodium or potassium salts, followed by subsequent reaction with zinc sulfate, zinc chloride, etc., respectively. Nevertheless, these carbonates have the drawback, in their most obtainable commercial form, of lack of homogeneity and varying composition, which is even more noticeable when they are to be reacted with weak organic acids, making the purification of the end product to improve its quality more elaborate. Detailed Description of the Invention. To overcome the above drawbacks, research has been directed to the development of new operative methods and it has been discovered that when zinc hydroxide, a homogenous product having a defined composition, is used, the end product may be produced not only with the absence of other contaminating anions, but also with a superior quality, not needing additional manipulation. The process of the invention is characterised in that equimolar amounts of acexamic acid and zinc hydroxide, or a slight excess of the former, are reacted in a polar solvent or mixture of solvents, preferably water. The temperature may be up to the boiling point of the solvent, preferably a temperature lying between 80 and 90°C is used. The acid may first be dissolved in the solvent, with the zinc hydroxide being added portionwise or in slurry or suspension form once the reaction temperature has been reached. Also, a suspension mixture of acid and hydroxide may be prepared in the solvent, followed by heating to reaction temperature. The salt may be isolated by crystallisation in the same solvent, or by adding another solvent in which it is less soluble, to increase the yield. The product is finally filtered and dried. Examples of application of the Invention. To facilitate the explanation, the invention is illustrated by, but not limited to, the following Examples: Example 1 3.46 g (20 mmoles) of acexamic acid were dissolved in 8 ml of distilled water. The solution was heated to 90°C and a slurry formed by 0.99 g (10 mmoles) of zinc hydroxide was gradually added. After the addition was over, the mixture was allowed to react with stirring for 15 minutes at that temperature, after which it was allowed to cool to room temperature. Thereafter it was cooled to 5°C. It was allowed to rest for 12 hours at this temperature, was filtered, washed and dried at 60°C. In this way, a white crystalline powder, zinc acexamate was obtained. Melting point: 193-196°C. Elementary analysis for C₁₆H₂₈N₂O₆Zn: C H N Zn Calculated (%) 46.94 6.84 6.84 15.96 Found (%) 47.08 6.95 6.80 15.85 Example 2 3.46 g (20 mmoles) of acexamic acid and 0.99 g (10 mmoles) of zinc hydroxide were poured into a flask containing 10 ml of distilled water. The temperature was raised to 90°C and held for 30 minutes. The mixture was allowed to cool to room temperature and was thereafter cooled to 5°C. It was allowed to stand at that temperature for 12 hours, was filtered, washed and dried at 60°C. In this way a white crystalline powder having the same characteristics as the one obtained following Example 1 was obtained.

Claims: A process for the preparation of an acexamic acid derivative, namely the zinc salt of formula: [CH₃ - CONH - (CH₂)₅ - COO]₂ Zn characterised in that acexamic acid is reacted with zinc hydroxide in a polar solvent. The process of claim 1, characterised in that said solvent is water. The process of claim 1 or 2, characterised in that the reaction temperature is equal to or lower than the boiling point temperature of the solvent. The process of any one of the foregoing claims, characterised in that the zinc salt obtained is isolated by crystallisation in the same solvent, followed by filtration and drying.

Inventors: BUXADE VINAS, ANTONIO, Buxadé Vinas, Antonio
Applicants: LABORATORIOS VINAS S.A.
Application year: 1989
Main classification: C07C233
IPC codes: C07C231, C07F3, C07C233