A kind of synthetic method of fluorine-containing glycine ester derivative

Abstract

The invention discloses a method for synthesizing fluorine-containing glycine ester derivatives. The steps are as follows: adding copper trifluoromethanesulfonate and glycine ester derivatives in proportion, using dichloromethane as a solvent, stirring for 30 min in an oxygen atmosphere, and then Add difluoroenol silyl ether in proportion; react at a certain temperature, wash with saturated brine after the reaction, add ethyl acetate for extraction, dry and filter the obtained organic phase, and distill off the solvent under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain fluorine-containing glycine ester derivatives. The present invention uses green and high-efficiency oxygen as an oxidant, which is cheap and easy to obtain compared with traditional oxidants; and does not require pre-preparation of raw material imines, and directly starts from glycine ester hydrocarbons, which meets the requirements of atom economy; the reaction conditions Mild, high yields can be achieved at room temperature.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a preparation method of a fluorine-containing glycine ester derivative. Background technique [0002] The introduction of one or several fluorine atoms into organic compounds can usually significantly improve the physical, chemical and biological activities of the compounds, and has become a commonly used molecular modification method in medicinal chemistry. Many studies have shown that the introduction of geminal difluoromethyl (CF 2 ), not only enhanced the acidity of its vicinal functional group, but also greatly improved the lipophilicity, metabolic stability and bioavailability of the drug parent molecule. For example, the geminal difluoroketone derivative is an important HIV-1 aspartate protease inhibitor, and the strong electro-withdrawing effect of the geminal difluoromethyl group enhances the electrophilicity of the vicinal carbonyl group and stabilizes the hydrated pro...

AI Technical Summary

Problems solved by technology

Among them, method (1) uses a toxic and unstable halogenated difluoroalkylation reagent, and another raw material imine needs to be prepared from aldehyde or amine in advance; method (2) α-haloglycinate is not easy to obtain, The amino acid needs to be prepared by halogenation or multi-step reaction, the preparation process produces a large amount of toxic waste, and the reaction yield is not high, and the scope of substrate application is limited; method (3) The key steps in the reaction require strong base, -78 o C low temperature condition