- Total synthesis method of bestatin
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The method comprises the following steps: (4 - chlorophenyl) (2 - pyridyl) - methanol as a starting raw material, and sequential addition reaction. Examples of the etherification reaction include a deprotection reaction, a chiral resolution, a condensation reaction, a hydrolysis reaction, and the like. The synthesis method has the advantages of cheap and easily available raw materials, no need of expensive chiral catalysts, simpler synthesis method, mild conditions, less side reactions and low cost.
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Paragraph 0020; 0050; 0054-0055; 0066; 0070-0071
(2021/10/11)
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- IMPROVED PROCESS FOR THE MANUFACTURE OF BEPOTASTINE AND ITS BESILATE SALT
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The present invention discloses a process for preparation of Bepotastine and its Besilate salt of formula I with good yield and purity. The invention also describes a process for recycle and reuse of the Ethyl-4-hydroxy piperidine-1-carboxylate from the aqueous medium after isolating the 2-[(S)-(4-Chlorophenyl)(piperidin-4- yloxy)methyl]pyridine, for subsequent batches in the production of Ethyl 4-[(4- Chlorophenyl)(pyridin-2-yl)methoxy]piperidine-1-carboxylate. The invention further discloses novel intermediates, viz., 2-[Chloro(4- chlorophenyl)methyl]pyridine hydrochloride and bis{2-[(S)-(4- Chlorophenyl)(piperidin-4-yloxy)methyl]pyridine} Dibenzoyl tartrate, useful in the preparation of Bepotastine and its Besilate salt.
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- Method for preparing bepotastine besilate key intermediate
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The invention relates to a method for preparing a bepotastine besilate key intermediate, in particular to 4-[(4-chlorphenyl)(2-pyridyl)methoxyl]piperidine-1-formate prepared from alpha-(4-chlorphenyl)-2-pyridinemethanol and 4-halogenated piperidine-1-carb
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Paragraph 0018
(2019/04/26)
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- Preparation method of 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine
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The invention discloses a preparation method of 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine. The method comprises the steps that alpha-(4-chlorobenzene ring)-2-pyridinemethanol and N-carbethoxy-4-pipradrol are adopted as starting raw materials, firstly, alpha-(4-chlorobenzne ring)-2-pyridinemethanol and N-carbethoxy-4-pipradrol are subjected to an etherification reaction under the catalysis of concentrated sulfuric acid to generate 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine-1-ethyl formate, then, the 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine-1-ethyl formate and sodium hydroxide are subjected to a hydrolysis reaction to generate a crude 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine, then, the crude 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine and fumaric acid form a salt to obtain a purified 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine fumarate, then, sodium hydroxide is used for ionization to finally obtain high-purity 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine. The method is easy to implement, low in cost, high in product yield and capable of facilitating industrial conversion.
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Paragraph 0023; 0024
(2017/02/09)
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- A novel synthetic method for bepotastine, a histamine H1 receptor antagonist
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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.
- Ha, Tae Hee,Suh, Kwee-Hyun,Lee, Gwan Sun
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p. 549 - 552
(2013/08/25)
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