668486-64-4Relevant academic research and scientific papers
PROCESS FOR PREPARING BEPOTASTINE AND INTERMEDIATES USED THEREIN
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Page/Page column 4-5, (2010/07/08)
A process for stereospecific preparation of bepotastine of formula (I) and novel intermediates used therein having formulae (II) to (IV) are provided. The inventive process comprises subjecting (RS)-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine to a reaction with a 4-halobutanoic acid l-menthyl ester, halo being chloro, bromo or iodo, in an organic solvent in the presence of a base to produce (RS)-bepotastine l-menthyl ester of formula (II), conducting a reaction of the compound of formula (II) with N-benzyloxycarbonyl L-aspartic acid in an organic solvent to induce selective precipitation of bepotastine l-menthyl ester.N-benzyloxycarbonyl L-aspartate of formula (III), filtering the precipitates formed in step 2) to isolate the compound of formula (III), treating the compound of formula (III) with a base to liberate bepotastine l-menthyl ester of formula (IV), and hydrolyzing the compound of formula (IV) in the presence of a base. The inventive process can provide bepotastine having a high optical purity of not less than 99.5% in a high yield, and thus, is useful in the development of anti-histamines and anti-allergic agents.
Diastereoselective synthesis of tetrahydrofurans from Aryl 3-chloropropylsulfoxides and aldehydes
Komsta, Zofia,Barbasiewicz, Michal,Makosza, Mieczyslaw
supporting information; experimental part, p. 3251 - 3259 (2010/08/19)
Carbanions of aryl 3-chloropropylsulfoxides react with nonenolizable aldehydes to give 2,3-disubstituted tetrahydrofurans. Deprotonation of the sulfoxides carried out in the presence of aldehydes results in the addition of the carbanions to the carbonyl group of the aldehydes, followed by 1,5-intramolecular substitution of the resulting aldol-type anion to produce the tetrahydrofuran ring. The 2-aryl and 3-arylsulfinyl substituents are always in trans relation, and the reaction proceeds with high diastereoselectivity also in respect to the chiral sulfur atom. The diastereoselectivity is attributed to the cyclic transition state of the aldol addition and increases when the aromatic ring of the sulfoxide contains electron-withdrawing substituents, whereas that of the aldehyde has electron-donating groups.
PROCESS FOR PREPARING BEPOTASTINE AND INTERMEDIATES USED THEREIN
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Page/Page column 8, (2009/01/24)
A process for stereospecific preparation of bepotastine of formula (I) and novel intermediates used therein having formulae (II) to (IV) are provided. The inventive process comprises subjecting (RS)-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine to a reaction with a 4-halobutanoic acid l-menthyl ester, halo being chloro, bromo or iodo, in an organic solvent in the presence of a base to produce (RS)-bepotastine l-menthyl ester of formula (II), conducting a reaction of the compound of formula (II) with N-benzyloxycarbonyl L-aspartic acid in an organic solvent to induce selective precipitation of bepotastine l-menthyl ester?N-benzyloxycarbonyl L-aspartate of formula (III), filtering the precipitates formed in step 2) to isolate the compound of formula (III), treating the compound of formula (III) with a base to liberate bepotastine l-menthyl ester of formula (IV), and hydrolyzing the compound of formula (IV) in the presence of a base. The inventive process can provide bepotastine having a high optical purity of not less than 99.5% in a high yield, and thus, is useful in the development of anti-histamines and anti-allergic agents.
