NOVEL METHOD OF PRODUCING TIOTROPIUM SALTS Russian patent published in 2010 - IPC C07D275/00 C07D491/08 A61K31/46 A61P11/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel method of producing tiotropium salts of formula 1 , in which X^- can denote a monovalent anion, preferably an anion selected from a group which includes chloride, bromide, iodide, methane sulphonate and trifluoromethane sulphonate, distinguished by that compounds of formula 2 , in which X^-can assume values given above, are reacted in a single stage in an acceptable solvent while adding an acceptable base to form a compound of formula 3 in situ, where R is a residue selected from a group which includes N-imidazolyl, N-triazolyl, -O- C(=NR')-NHR", -O-SO₂-phenyl, -O-SO₂-phenylmethyl, -O-SO₂-R', -O-CO-C(methyl)₃, -O-CO-phenyl-NO₂, chlorine, bromine, -N₃ and -O-(P=O)R'" where R' denotes C₁-C₄alkyl or C₃-C₆cycloalkyl, R" denotes C₁-C₄alkyl, C₃-C₆cycloalkyl or C₁-C₄alkylene- N(C₁-C₄alkyl)₂, and R'" denotes C₁-C₄alkyl, -O-C₁-C₄alkyl, phenyl or -O-phenyl, and R¹ and R² have identical or different values and can be methyl, ethyl, propyl, butyl or phenyl which can optionally be substituted with one or more C₁-C₄alkyl residues to obtain a compound of formula 4 , in which groups X^-, R¹ and R² can assume values given above, and then without its extraction, the compound of formula 4 is reacted with an acceptable acid or with an acceptable desilylation agent with removal of the silyl group in the compound of formula 1. The invention also relates to compounds of formulae 3 and 4.

EFFECT: obtaining tiotropium salts of formula 1 using a simpler and more efficient method which increases output of the product.

8 cl, 9 ex