- Synthesis of 2,2-difluoro-2-arylethylamines as fluorinated analogs of octopamine and noradrenaline
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A series of 2,2-difluoro-2-arylethylamines was synthesized as fluorinated analogs of octopamine and noradrenaline with the expectation of bioisosteric OH/F exchanges. The syntheses of these compounds were performed by a Suzuki-Miyaura cross-coupling reaction of 4-(bromodifluoroacetyl)morpholine with aryl boronic acids to produce the intermediate 2,2-difluoro-2-arylacetamides, followed by transformation of difluoroacetamide to difluoroethylamine.
- Tarui, Atsushi,Kamata, Erika,Ebisu, Koji,Kawai, Yui,Araki, Ryota,Yabe, Takeshi,Karuo, Yukiko,Sato, Kazuyuki,Kawai, Kentaro,Omote, Masaaki
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- Lewis acid-mediated defluorinative [3+2] cycloaddition/aromatization cascade of 2,2-difluoroethanol systems with nitriles
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The properties of C?F bonds, including high thermal and chemical stability, make derivatization of organic fluorine-containing compounds by the activation of the C?F bond and subsequent functionalization quite challenging. We herein report a Lewis acid-mediated defluorinative cycloaddition/aromatization cascade of 2,2-difluoroethanols with nitriles as a novel synthetic method for the preparation of 2,4,5-trisubstituted oxazoles. This reaction, which involves cleavage of two C?F bonds and the consecutive formation of C?O and C?N bonds in a one-pot fashion, features a broad substrate scope and moderate to high reaction yields. Mechanistic studies revealed that the reaction is initiated by the Lewis acid-mediated ring closure of the 2,2-difluoroethanol to produce the fluoroepoxide intermediate. (Figure presented.).
- Hsieh, Min-Tsang,Lee, Kuo-Hsiung,Kuo, Sheng-Chu,Lin, Hui-Chang
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p. 1605 - 1610
(2018/03/05)
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- Preparation of difluorinated alcohol compound
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The present invention relates to a method for producing a difluoro alcohol compound. According to the present invention, compared to prior arts, the method for producing the difluoro alcohol compound is simple, safe, and cost-competitive in terms of a use of reagents, since a synthesis is simply carried out via a reaction between N-fluorobenzenesulfonimide and aldehyde in the presence of L-proline. Accordingly, the method of the present invention can be effectively applied to the production of the difluoro alcohol which gives a wide range of applications such as functional drugs, pesticides, and raw materials for polymeric compounds.COPYRIGHT KIPO 2017
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Paragraph 0126; 0127
(2017/04/25)
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- β,β-Difluoro analogs of α-oxo-β-phenylpropionic acid and phenylalanine
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A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes (2) into α-aryl-α,α- difluoroacetaldehydes (1). Subsequent hydrocyanation, hydrolysis, oxidation and again hydrolysis afforded β-aryl-β,β-difluoro-α- oxopropionic acids (3). Reductive amination transformed the oxoacids 3 into a separable mixture of α-hydroxyacids 11 and racemic β,β-difluoro- β-phenylalanine derivatives (4). Enantiomerically pure β,β- difluorophenylalanine (L-4a) was obtained when α,α-difluoro-α- phenylacet-aldehyde (1a) was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixture thus produced hydrolyzed to the carboxamides (15) which were found to be separable by fractional crystallization or chromatography. The pKa values of the β-aryl-β,β-difluoroalanines (4) were measured and biological profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid (4c) proved to be a potent (Ki 27 μM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis.
- Schlosser, Manfred,Brügger, Nadia,Schmidt, Werner,Amrhein, Nikolaus
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p. 7731 - 7742
(2007/10/03)
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