Patent ID: 6642364
Filing Date: 2003-11-04
Classification: C07H

Abstract:
A process for producing clarithromycin comprising the steps of:(a) reacting erythromycin A 9-oxime hydrochloride with 1,1-diisopropoxycyclohexane in the presence of a catalytic amount of a pyridine salt, in methylene chloride as a solvent, so as to obtain a mixed acetal; (b) reacting hexamethyldisilazane and imidazole in the presence of sulfuric acid, and thereafter adding chlorotrimethysilane in methylene chloride as a solvent, so as to obtain a silylation agent; (c) reacting the resulting mixed acetal of step (a) with the resulting silylation agent of step (b) in methylene chloride as a solvent, so as to obtain erythromycin A 2â€²,4â€³-bis(trimethylsilyl)-9-[O-isopropoxycyclohexyl]oxime; (d) reacting the resulting erythromycin A 2â€²,4â€³-bis(trimethylsilyl)-9-[O-isopropoxycyclohexyl]oxime of step (c) with methyl iodide and potassium hydroxide in methylene chloride and dimethylsulfoxide as solvents, so as to obtain erythromycin A 2â€²,4â€³-bis(trimethylsilyl)-6-O-methyl-9-[O-isopropoxycyclohexyl]oxime; (e) deprotecting the resulting erythromycin A 2â€²,4â€³-bis(trimethylsilyl)-6-O-methyl-9-[O-isopropoxycyclohexyl]oxime obtained in step (d) in a solution of methanol, water and 85% formic acid, so as to obtain clarithromycin oxime; and (f) deoximating the resulting clarithromycin oxime of step (e) with aqueous sodium metabisulfite so as to obtain clarithromycin.