• Archives of Pharmacal Research
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• v.29 no.1
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• pp.108-111
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• 2006

The economic and effective method for preparation of R-(-)-ibuprofen by diastereomer crystallization was developed. R-(-)-ibuprofen was resolved from racemic ibuprofen by forming R-(-)ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt with R-(+)-$\alpha$-methylbenzylamine and crystallization. The purity of R-(-)-ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt was tested and confirmed using HPLC and $^1H-NMR$ method. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to the pure enantiomer without racemization. R-(-)-ibuprofen was recovered producing overall yield of 2.4% with the purity more than 99.97%.

• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.549-552
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• 2013

An efficient and alternative synthesis of enantiomerically pure (+)-(S)-4-(4-((4-chlorophenyl)(pyrid-2-yl)methoxy]piperidin-1-yl)butanoic acid, bepotastine (1) is described. The key resolution of (R/S)-bepotastine l-menthyl ester (3) is achived via diastereomeric salt crystallization using N-benzyloxycarbonyl-L-aspartic acid (NCbzLAA) as the resolving agent to provide (S)-bepotastine l-menthyl ester (S)-3. Hydrolysis of (S)-bepotastine l-menthyl ester (S)-3 afforded the desired bepotastine (1) with good yields and enantiopurity (> 99%). Finally, bepotastine besilate (4) and bepotastine calcium (5) are achived by salt formation of bepotastine (1) with benzene sulfonic acid and calcium salt respectively. The reaction conditions were optimized to make suitable for commercial scale production.

• Journal of the Korean Chemical Society
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• v.55 no.6
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• pp.940-951
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• 2011

Reaction of 1-methylpyrimidine-(1H,3H,5H)-2,4,6-trione (1-MBA 1) as an unsymmetrical barbituric acid with cyanogen bromide and various aldehydes in the presence of triethylamine and/or pyridine afforded diastereomeric mixtures of new class of heterocyclic stable 5-aryl-1,1'-dimethyl- and 5-aryl-3,1'-dimethyl-1H,1'H-spiro[furo[2,3-d]pyrimidine-6,5'-pyrimidine]2,2',4,4',6'(3H,3'H,5H)-pentaones which are dimeric forms of 1-methyl barbiturate at the range of $0^{\circ}C$ to room temperature. In the reaction of some aldehydes with 1-MBA and BrCN were afforded a mixture of diastereomers. Another two aldehydes such as 4-cyano- and 2-hydroxybenzaldehydes gave exclusively two diastereomers in which binded to the salt of triethylammonium hydrobromide by intermolecular H-bond in ratio of 1:1. 4-Hydroxybenzaldehyde and 2-pyridinecarbaldehyde gave exclusively one diastereomer under the same condition. Aldehydes possessing strong electron-donor were produced exclusively two geometric isomers of Knoevenagel adduct (E- and Z-isomers). The structures of compounds were deduced by $^1H$ NMR, $^{13}C$ NMR and FT-IR spectroscopy. Mechanism of the formation is discussed.

• Journal of the Korean Chemical Society
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• v.59 no.6
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• pp.488-492
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• 2015

In this study, the effective preparation method of (S)-(+)-pranidipine, the active component of antihypertensive drug as a calcium channel blocker, was developed using optical resolution. The racemic monocarboxylic acid 5 obtained by the hydrolysis of (±)-pranidipine was mixed with optically active quinidine to form salts, and the insoluble diastereomeric salt was collected and successive treatment with base and acid furnished (R)-(-)-carboxylic acid 7. (S)-(+)-Pranidipine was prepared by esterification of this acid with cinnamyl alcohol, and the analysis by chiral HPLC showed 100% enantiomeric excess (ee). This process would be industrially very useful to prepare chiral (S)-(+)-pranidipine, since the use of strong base and anhydrous solvents, and ultra-low temperature condition were excluded in this process.