METHOD OF PREPARING AZITROMICYN AND METHODS FOR PRODUCTION OF INTERMEDIATES Russian patent published in 2000 - IPC

FIELD: pharmaceutical chemistry. SUBSTANCE: method is distinguished by that erythromycin is converted to oxime by hydroxylamine hydrochloride in presence of sodium carbonate in aqueous ethanol (20-40% water) medium at starting erythromycin-to-solvent g/ml ratio from 1:1.4 to 1:1.7 at temperature 50-80 C. Oxime product is isolated from reaction mixture by extraction with chlorinated hydrocarbon at pH 9-11 and subjected to Beckmann rearrangement by agency of arenesulfonic acid chloride in two-phase water-chlorinated hydrocarbon system to form erythromycin imino-ester. The latter is isolated by crystallization at pH 9-11 and temperature 60+-5 C and reduced in aqueous medium at room temperature with 0 to 0.2 molar excess of complex metal borohydride to give azaerythromycin. The latter is methylated, in the form of borate complex with mineral or organic acid (preferably, hydroxyacid), at pH 2.5, with formaldehyde in chloroform in presence of formic acid. Methylation product is isolated by reextraction with water at pH 4.5-5.5. Borate complex, if necessary, is hydrolyzed and product is precipitated form aqueous solution at pH 9-11 and 50-80 C and then recrystallized from acetone-water (2:1 to 1:2) mixture. EFFECT: simplified process and increased yield of final product. 4 cl, 5 ex