1,2-Dimethoxyethane → 2,2,2-Trifluoro-1-(pyrazin-2-yl)ethan-1-one

Participants

Reaction Steps

A solution of pyrazine carboxylate methyl ester is dissolved in an inert solvent, for example monoglyme (dimethoxyethane). To this solution is added a mixture of trimethylsilyltrifluoromethane and dry caesium fluoride. After about 12-24 hours, at a temperature of about room temperature, the solvent is removed under reduced pressure. The residue is dissolved in a mixture of an inert solvent, for example tetrahydrofuran, and an organic acid, for example acetic acid, and the mixture is treated with tert-butylammonium fluoride. The reaction is conducted at a temperature of about room temperature for about 3 hours. When the reaction is substantially complete, the compound of formula (18) is isolated by conventional means, for example by diluting with water, extracting the product into an inert solvent, for example ethyl acetate, washing with a solution of a mild inorganic base, for example sodium bicarbonate, and drying. Removal of the solvent under reduced pressure provides a crude compound, which can be purified by trituration with an inert solvent, for example a mixture of dichloromethane and hexane, to give a compound of formula (18), 2,2,2-trifluoro-1-(pyrazin-2-yl)ethanone.

Provenance & Evidence