- Semi-Industrial Fluorination of β-Keto Esters with SF 4: Safety vs Efficacy
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The possibility of deoxofluorination of β-keto esters using SF 4 was investigated. The scope and limitation of the reaction were determined. The efficient method for the synthesis of β,β-difluorocarboxylic acids was elaborated based on the reaction. The set of mentioned acids, being the perspective building blocks for medicinal chemistry, were synthesized on multigram scale. The safety of SF 4 use was discussed. The described method does not improve upon the safety of using SF 4, but practical recommendations for working with the reagent are proposed. Despite the hazards of using toxic SF 4, a significant increase of efficacy in the synthesis of medicinal-chemistry-relevant building blocks, based on the reaction, in comparison with earlier described approaches is shown.
- Bugera, Maksym Y.,Khairulin, Andrii R.,Kliukovskyi, Denys V.,Ryabukhin, Sergey V.,Semenov, Sergey V.,Shevchenko, Valerii O.,Tarasenko, Karen V.,Trofymchuk, Serhii A.,Volochnyuk, Dmitriy M.
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p. 565 - 574
(2020/03/27)
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- Method for synthesizing beta-difluorocarboxylic acid from beta-keto ester
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The invention relates to a method for synthesizing a beta-difluorocarboxylic acid compound from beta-keto ester, to solve the technical problems that the yield is low and the production cannot be enlarged in most methods at present. According to the technical scheme of the invention, the method for synthesizing the beta-difluorocarboxylic acid from the beta-keto ester is characterized by comprising the following steps: carrying out a reaction between beta-keto acid ester, which is used as a raw material easily available in the market, and SF4 in the presence of HF to generate beta-difluorocarboxylic ester, and hydrolyzing the beta-difluorocarboxylic ester under an acidic condition to obtain the beta-difluorocarboxylic acid. The molecules and derivatives thereof involved in the invention may be involved in synthesis of an inhibitor of phosphodiesterase (PDEs), particularly PDE2.
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Paragraph 0014
(2018/05/01)
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