Patent ID: 8471030

Claim:
A continuous process for the purification of a crude Montelukast sodium mixture comprising Montelukast sodium-trans and impurities comprising Montelukast sodium-cis, Montelukast sodium-sulfoxide, Montelukast sodium-styrenic impurities, other impurities, in an organic solvent to provide a purified Montelukast sodium-trans product, said process comprising: a. combining the crude Montelukast sodium mixture with deionized water to provide a feed mixture comprising deionized water, the organic solvent, Montelukast sodium-trans, Montelukast sodium-cis, Montelukast sodium-sulfoxide, Montelukast sodium-styrenic impurities and the other impurities, said feed mixture having a pH greater than or equal to 8.5 and less than 12, said feed mixture comprising from about 2.5 to about 10 wt-% of the crude Montelukast mixture in deionized water and filtering the feed mixture in a filtration zone to provide a filtered feed mixture; b. passing the filtered feed mixture and at least one mobile phase desorbent comprising methanol having a pH of between 8 and 12, to a simulated moving bed (SMB) system having a first SMB zone operating in a rejection mode and a second SMB zone operating in an extraction mode, said SMB system comprising a complex valve system and a plurality of adsorbent beds containing a stationary phase adsorbent selected from the group consisting of C4 adsorbent, C8 adsorbent, C18 adsorbent, and basic alumina and being selective for the separation of Montelukast sodium-trans from at least one of said impurities in the absence of light and at an SMB temperature of from 10 to 30° C. and at an SMB pressure effective to maintain liquid phase, wherein the stationary phase adsorbent and the at least one mobile phase desorbent are directed to flow in a counter-current manner by the complex valve system to provide a Montelukast sodium-trans rich extract stream, comprising Montelukast sodium-trans, mobile phase desorbent, and less than 0.5 wt-% water and a waste impurity stream comprising said mobile phase desorbent, Montelukast sodium-cis, Montelukast sodium-sulfoxide, the Montelukast sodium-styrenic impurities and the other impurities; c. passing the Montelukast sodium-trans rich extract stream comprising Montelukast sodium-trans and mobile phase desorbent to an evaporization zone operating at an evaporization temperature less than about 50° C. to recover the mobile phase desorbent and to provide an evaporated extract stream; d. stripping the evaporated extract stream with a hydrocarbon solvent to provide a stripped evaporated extract stream; and, e. passing the stripped evaporated extract stream to a crystallization zone and therein contacting the stripped evaporated extract stream with the hydrocarbon solvent selected from the group consisting of hexane, heptane, toluene and mixtures thereof at effective crystallization conditions and withdrawing the purified Montelukast sodium-trans product having a Montelukast purity of greater than or equal to 99.5 wt-%.