Method for fluoromethylation of alcohols via halogenative...

C - Chemistry – Metallurgy – 07 – C

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C07C 41/22 (2006.01) C07C 43/12 (2006.01)

Patent

CA 2410428

A method for fluoromethylation of an alcohol via halogenative decarboxylation. The method includes the step of reacting an alcohol of the formula R1C(CX3)2OH with an alpha- haloester of the formula X2CH2CO2R2 to form an alpha-alkoxy ester, wherein R1 is selected from the group consisting of hydrogen and alkyl groups, wherein R2 is selected from the group consisting of hydrogen and alkyl groups, wherein X, at each occurrence, is independently selected from the group consisting of hydrogen, bromine, fluorine, and chlorine, and wherein X2 is selected from the group consisting of bromine and chlorine. The resulting alpha-alkoxy ester is saponified to form an alpha-alkoxy acid which is heated at reflux with lead tetraacetate and a chlorinating agent to form a chloride compound of the formula R1C(CX3)2OCH2Cl. The chloride compound is converted to a fluoride compound of the formula R1C(CX3)2OCH2F with a fluorinating agent.

L'invention concerne un procédé de fluorométhylation d'un alcool par décarboxylation à effet halogénant. Ce procédé comprend la phase de réaction d'un alcool de formule R?1¿C(CX¿3?)¿2?OH avec un alpha-haloester de formule X?2¿CH¿2?CO¿2?R?2 ¿pour former un ester d'alpha-alkoxy, où R?1¿ est choisi dans le groupe comprenant des groupes hydrogène et alkyle, R?2¿ est choisi dans le groupe comprenant des groupes hydrogène et alkyle, X, à chaque apparition, est choisi indépendamment du groupe comprenant hydrogène, brome, fluor, et chlore, et X?2¿ est choisi dans le groupe comprenant brome et chlore. L'ester d'alpha-alkoxy en résultant est saponifié pour constituer un acide d'alpha-alkoxy qui est chauffé à reflux avec du tétra-acétate de plomb et un agent chlorant pour former un composé chlorure de formule R?1¿C(CX¿3?)¿2?OCH¿2?C1. Ce composé chlorure est transformé en un composé fluorure de formule R?1¿C(CX¿3?)¿2?OCH¿2?F avec un agent fluorant.

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