METHOD OF PRODUCING SODIUM SALT OF 1-[[[(R)-M-[(E)-2-(7-CHLORO-2-QUINOLYL)VINYL]-ALPHA-[O-(1-HYDROXY-1-METHYLETHYL)PHENETYL]BENZYL]THIO]METHYL]CYCLOPROPANE ACETIC ACID Russian patent published in 2011 - IPC C07D215/18 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel method of producing a sodium salt of 1-[[[(R)-M-[(E)-2-(7-chloro-2-quinolyl)vinyl]-alpha-[O-(1-hydroxy-1-methylethyl)phenetyl]benzyl]thio]methyl]cyclopropane acetic acid (Montelukast sodium), which involves the following steps: a) reaction of 2-(2-(3(S)-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-hydroxypropyl)phenyl)-2-propanol with methane sulphonyl chloride in the presence of a tertiary amine, b) filtering the crude solution of methane sulphonate 2-(2-(3(S)-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-hydroxypropyl)phenyl)-2-propanol obtained at step a) from solid amine hydrochloride and direct reaction with a disodium salt of 1-(mercaptomethyl)cyclopropane acetic, c) extraction of 1-[[[(R)-M-[(E)-2-(7-chloro-2-quinolyl)vinyl]-alpha-[O-(1-hydroxy-1- methyethyl)phenetyl]benzyl]thio]methyl]cyclopropane acetic acid from the reaction mixture obtained at step b) in form of a toluene solution. That solution is then treated with tert-butylamine, thereby obtaining tert-butylamine salt of 1-[[[(R)-M-[(E)-2-(7-chloro-2-quinolyl)vinyl]-alpha-[O-(1-hydroxy-1-methylethyl)phenetyl]benzyl]thio]methyl]cyclopropane acetic acid in crystalline form, d) extraction and purification of the salt obtained at step c), e) turning the salt obtained at step d) into an amorphous sodium salt of 1-[[[(R)-M-[(E)-2-(7-chloro-2-quinolyl)vinyl]-alpha-[O-(1-hydroxy-1-methylethyl)phenetyl]benzyl]thio]methyl]cyclopropane acetic acid.

EFFECT: novel method of producing Montelukast sodium, characterised by considerable simplification of the production process.

4 cl, 5 dwg, 2 ex