METHOD FOR PREPARING CLARITHROMYCIN AS CRYSTALS OF FORM II Russian patent published in 2004 - IPC

FIELD: pharmaceutical technology, pharmacy, antibiotics.

SUBSTANCE: clarithromycin as crystals of form II of the formula (I)

is prepared by treatment of clarithromycin with methanesulfonic acid in mixture of water-soluble organic solvent and water that results to formation of crystalline clarithromycin trihydrate mesylate of the formula (II)

that is subjected for neutralization with ammonia aqueous solution in mixture of water-soluble organic solvent and water. Clarithromycin no exhibiting the pharmaceutical purity index is prepared by protection of 9-oxime hydroxy-group of erythromycin A 9-oxime or its salt with tropyl group, and 2'- and 4''-hydroxy-groups are protected with trimethylsilyl group to yield 2',4''-O-bis-(trimethylsilyl)-erythromycin A 9-O-tropyloxime that is subjected for interaction with methylating agent to yield 2'.4''-O-bis-(trimethylsilyl)-6-O-methylerythromycin A 9-O-tropyloxime followed by removal of protective groups and oxime group. Invention relates also to intermediate compounds of the formula (II) and the formula (III)

wherein R¹ represents hydrogen atom or methyl group; R² represents hydrogen atom or trimethylsilyl group wherein if R¹ represents methyl group then R² represents trimethylsilyl group. Method provides enhancing yield and improving purity of the end product.

EFFECT: improved preparing method.

16 cl, 3 tbl, 4 dwg, 23 ex