![]() Synthesis of Enantiomerically Enriched Cetirizine. E-mail:, † Department of Analytical Chemistry. Herein, we disclose an economic and operationally simple technology for the separation of the enantiomers of cetirizine utilizing chiral HPLC of the inexpensive and readily available amide 5. To develop a practical chiral separation, the separation must be (1) performed with an inexpensive and readily available compound,4 (2) efficient (have a large R value and high loading capacity), and (3) cost-competitive with a resolution or asymmetric synthesis. Recently, we disclosed synthesis of both enantiomers of cetirizine by addition of phenylmagnesium bromide or phenyllithium to a chiral imine.3 While this approach is appealing, a more economic and scalable route was desired. The low-yielding resolutions led us to concentrate on asymmetric synthesis and preparative chiral HPLC. The reported syntheses of singleenantiomer cetirizine require either a low-yielding resolution of a cetirizine precursor1 or the use of a stoichiometric heavy metal.2 We sought an alternative approach that would allow access to either enantiomer of cetirizine in a rapid fashion. Introduction Racemic cetirizine dihydrochloride (1, sold under the trade name Zyrtec is a second generation H1 receptor antagonist antihistamine (replacing the sedating hydroxazine), and evidence suggests that the levorotatory (S) enantiomer of cetirizine displays an improved pharmacological profile compared to the racemate. ![]() ![]() ![]() The amide has an r value of 2.76 (USP resolution of 8.54) using a Chiralpak AD column, and 0.5 wt % of the amide (based on packing material) can be injected per run. Wald Sepracor, Inc., Chemical Research and DeVelopment, 111 Locke DriVe, Marlborough, Massachusetts 01752Ībstract: Enantiomerically pure cetirizine can be prepared by preparative HPLC separation of cetirizine amide. Organic Process Research & Development 2001, 5, 110−115Īrticles A Large-Scale Synthesis of Enantiomerically Pure Cetirizine Dihydrochloride Using Preparative Chiral HPLC Derek A. ![]()
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