METHOD OF SYNTHESIS OF 2-OXO-4-PHENYLBUTYRIC ACID FROM ETHYLESTER OF 2,2-DIETHOXY-4-PHENYLBUTYLENIC ACID

A new method for the synthesis of 2-oxo-4-phenylbutanoic ethyl ester has been suggested, where respective butenoic and butanoic kethals are used as intermediate products. 2-oxo-4-phenylbutanoic ethyl ester is syntone for synthesis of enalapril and its analogues used in the treatment of cardiovascular diseases. Previous methods are hardly applicable for the production of syntone in greater amounts, because they are either based on distillation of substance in high vacuum or multistage process with the use of expensive chemicals. The proposed radically new method for production of syntone is based on the transformation of natrium salts of 2-oxo-4-phenylbutenoic acid in the respective kethalester, its hydrating to syntone kethal. Shortly before application of the syntone its kethal is hydrolysed with phosphoric acid to syntone. The products are stable in all stages, thus reaction is easily directed. Production of kethal, its hydrating and hydrolysis of saturated kethal result in a high outcome. The total outcome of syntone is up to 69%, which is considerably (by 29%) higher in comparison with the Grynjahr synthesis and 10% higher than using well-known methods. All stages can be carried out in the industrial production. Product is stored in the form of kethal, thus considerably reducing admixtures that arise during storage. It has also been discovered that acetonitrile increases hydrolisation speed of saturated kethal.