METHOD FOR PRODUCING THIOTROPIUM BROMIDE Russian patent published in 2017 - IPC C07D451/10 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel method for producing tiotropium bromide, comprising i) reacting scopine oxalate (X) with diethylamine in an inert solvent at a temperature of about 30°C to about 45°C with the formation of skopin; ii) reacting scopin and methyl di-(2-dithienyl)glycolate (MDTG) in the presence of an inorganic base selected from anhydrous potassium carbonate, anhydrous cesium carbonate or potassium tert-butoxide and in an inert solvent at a temperature between about 80°C and about 110°C with formation of N-demethyltiotropium; iii) reacting N-demethyltiotropium with bromomethane in an inert solvent at a temperature of about 0°C to about 25°C with the formation of tiotropium bromide; iv) crystallizing tiotropium bromide in a mixture of methanol and acetone, and optionally thereafter v) micronizing thus produced tiotropium bromide.

EFFECT: increasing the yield.

31 cl, 11 dwg, 1 tbl, 4 ex