Hypolipaemic magnesium (4)-chloro-phenoxy-isobutyrate prodn. - by reacting (4)-chloro-phenoxy-isobutyric acid with magnesium oxide in water or aqueous acetone COE 15.4.77)

摘要

In a new process for the prepn. of p-chlorophenoxyisobutyric acid Mg salt (I), p-chlorophenoxyisobutyric acid or its NH4 salt is reacted with heating with magnesium oxide in the presence of water or a mixt. of acetone and water. In an example, a solution of 43g p-chlorophenoxyisobutyric acid in 40g acetone and 4g demineralized water treated with a slurry of 4g MgO in 60g demineralised water and refluxed for ca 0.5 hr. After crystallising in a refrigerator, crystals are filtered off and dried to give (I) (26.7g). Further 32g (I) is determined from the mother liquors. (I) is a known (DT 2308331) hypolipaemic agent which is more effective and better tolerated than the corresponding free acid or its ethyl ester (clofibrate). Use of magnesium oxide avoids introducing foreign ions into the reaction mixture, and (I) is obtained in pure crystalline form. Yields of 90% or more obtained, and the cost of magnesium oxide is low. The product obtained is stable and has a high melting point, so that it can be incorporated into pharmaceutical formulations without difficulty.