BigPatents India

A process for direct preparation of highly pure above 98% 6-O-methyl erythromycin A (Clarithromycin) Form II from crude 6-O-methyl-N-demethylerythromycin A, comprising of I) purification of crude 6-O-methyl-N-demethylerythromycin A by at least partial dissolution and/or suspension in selective organic solvent system; ii) N-methylation of purified 6-0-methyl-N-demethylerythromycin A in presence of formic acid and atleast one of formaldehyde and paraformaldehyde in water miscible organic solvents; and iii) adjusting pH; and iv) isolating the highly pure 6-O-methylerythromycin A form II. Also disclosed is a simple, safe and cost-effective process for the manufacdture of highly pure 6-O-methylerythromycin A (Clarithromycin) Form II from erythromycin A-9-Oxime derivative and a process for direct conversion of pure 6-O-methyl-N-demethylerythromycin A of Formula II to pure 6-O methyl erythromycin A form II of Formula I. The above processes are high yielding, cost effective, easy to operate at industrial scale, be safe to carry out and without not involving carcinogenic, anesthetic and highly explosive solvents like chloroform and highly flammable diethyl ether and with provide purity as per established pharmacopoeial limits. The processes would provide industrially feasible large-scale preparation of clarithromycin Form II crystal. Drawing: 02 Sheets. Total Pages: 25. Fig. Nil