METHOD OF PRODUCING CALCIUM SALT (E)-7-[4-(4-FLUOROPHENYL)-6-ISOPROYL-2-[METHYL(METHYSUFONYL)AMINO]PYRIMIDIN-5-YL](3R,5S)3,5-DIHYDROXYHEPT-6-ENOIC ACID (ROSUVASTATIN CALCIUM SALT) Russian patent published in 2009 - IPC C07D239/42 

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing calcium salt (E)-7[4(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid (rosuvastatin calcium salt), suitable for making a pharmaceutical drug, useful in treatment of, among others, hypercholesteremia, hyperlipoproteinemia and atherosclerosis. The method involves stages (a)-(g): a) reaction of (1-6C)alkyl ester (E)-(6-{2-[4-(4-flurophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]vinyl}(4R,6S)-2,2-dimethyl[1,3]dioxin-4-yl)acetic acid in an organic solvent mixed with water with aqua acid at high temperature; b) reaction of the obtained solution with aqueous hydroxide of an alkali metal and, possibily, washing the obtained aqueous solution of salt of the alkali metal with a suitable organic solvent; c) bringing the pH of the obtained solution to approximately pH 9-10.5 by adding aqueous hydrochloric acid; d) removal of the organic solvent mixed with water; e) possible filtration of the obtained mixture; f) addition of water soluble calcium salt to the filtrate so that, calcium salt (E)-7[4(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(1R,5S)-3,5-dihydroxyhept-6-enoic acid is formed; and g) extraction of product of stage (f). The preferred organic solvent mixed with water is acetonitrile. Aqua acid on stage (a) is hydrochloric acid. Stage (b) involves reaction of the obtained solution with aqueous sodium hydroxide and washing the obtained aqueous solution of sodium salt with a suitable hydrocarbon, ester or ether solvent, for example, toluene, xylol, MTBE (methyl-tert-butyl ether) or ethyl acetate.

EFFECT: improved method.