- A ketotifen intermediate mother liquor recovery method
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The present invention provides a containing 10 - methoxy - 4 H - benzo [4, 5] [...] [1, 2 - b] thiophene - 4 - one mother liquor recovery method, the method comprises containing 10 - methoxy - 4 H - benzo [4, 5] [...] [1, 2 - b] thiophene - 4 - one stock solution dissolved in an organic solvent, temperature, to the reaction solution adding reducing agent in the reaction, after the reaction heat filter, concentrated to dry adding crystalline solvent crystallization, of high purity can be obtained 10 - methoxy - 4 H - benzo [4, 5] [...] [1, 2 - b] thiophene - 4 - one. The method can realize the 10 - methoxy - 4 H - benzo [4, 5] [...] [1, 2 - b] thiophene - 4 - one mother liquor of effectively recycling, and the reaction process is easy to control, and does not need of complex special equipment; in addition in the mother liquor of each the impurity reduction reaction conversion, can be by a simple crystallization method of separation and purification.
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Paragraph 0032; 0034
(2019/02/13)
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- A 10 - methoxy - 4 H - benzo [4, 5] cycloheptatriene [1, 2 - b] thiazole - 4 - ketone
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The present invention discloses a 10-methoxy-4H-benzo[4,5]cycloheptatriene[1,2-b]thiazol-4-one preparation method, which comprises: mixing a raw material 9,10-dihydro-9,10-dibromo-4H-benzo[4,5]cycloheptatriene[1,2-b]thiazol-4-one and absolute methanol, carrying out stirring reflux for 2-6 h, adding a solid alkali catalyst to the reaction solution, continuously carrying out the reflux reaction for 2-6 h, carrying out separation purification on the reaction solution after completing the reaction, and recovering the solid alkali catalyst so as to obtain the product 10-methoxy-4H-benzo[4,5]cycloheptatriene[1,2-b]thiazol-4-one. According to the present invention, the solid alkali catalysis is used, the technology is easy to operate, the equipment is not corroded, the three-waste is less, the post-treatment is easy, the solid alkali can be reused, and the preparation method is the economical and practical green environmental protection technology.
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Paragraph 0023; 0029-0030
(2018/06/19)
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- 4H-BENZOCYLOHEPTATHIOPHENES AND 9,10-DIHYDRO DERIVATIVES-SULFONIUM ANALOGUES OF PIZOTIFEN AND KETOTIFEN; CHIRALITY OF KETOTIFEN: SYNTHESIS OF THE 2-BROMO DERIVATIVE OF KETOTIFEN
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Reaction of ketone IX with 4-tetrahydrothiopyranylmagnesium bromide and the following dehydration with thionyl chloride afforded the sulfide III which was transformed to the methiodide II (sulfonium analogue of pizotifen).Similar sequence starting from ketone XXIV and concluded by dehydration of the alcohol XX, cleavage of the enol ether, and by treatment with methyl iodide resulted in the formation of the sulfonium analogue of ketotifen (V).Three modified routes leading to ketotifen (IV) are being described.The chirality of ketotifen was proven by (1)H NMR spectrscopy with the help of,optically active NMR shift reagent.The resolution of racemic ketotifen (IV) was achieved by crystallization of salts with optically active O,O'-diacyltartaric acids and homogenous anantiomers were obtained.The X-ray crystallographic analysis of (+)-IV-O,O'-di(p-toluoyl)-(R)-tartrate led to the three- dimensional structure of the molecule of (+)-ketotifen which enabled to determine its absolute configuration to be (R).One of the products of bromination of the ketone IX, the following methanolysis and dehydrobromonation, identified as XXVII, was transformed by reaction with 1-methyl-4-piperidylmagnesium chloride, by the following acid-catalyzed dehydration, and cleavage of the enol ether to the 2-bromo derivative of ketotifen XXXIV. (R)(+)-Ketotifen (IV) was found to be the more active ketotifen enantiomer but the stereoselectivity of its action is only a partial one.The 2-bromo derivative of ketotifen (XXXIV) is much less active than ketotifen in the line antihistamine activity.
- Polivka, Zdenek,Budesinsky, Milos,Holubek, Jiri,Schneider, Bohdan,Sediva, Zdenek,et al.
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p. 2443 - 2469
(2007/10/02)
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