Hydrochloric Acid → 1-(4-Fluorophenyl)-2-(4-methylthiophenyl)ethanone

Participants

Reaction Steps

To 321 ml of a 1.0M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (containing 321 mMol, 1.1 eqs) along with an additional 200 ml of dry tetrahydrofuran stirring at -70° C., was added dropwise a solution of 65.1 g (292 mMol) of (4-fluorophenyl)-2-trimethylsilyl-ethanenitrile from Step 1 in 100 ml of tetrahydrofuran. After stirring for 1 hour, a solution of 50.5 g (292 mMol, 1.0 eq) of (4-methylthiophenyl)chloromethane from Step 2 in 100 ml of tetrahydrofuran. The mixture was stirred overnight while warming to room temperature. To the mixture was then added 300 ml of 3N aqueous hydrochloric acid, and the resulting two phase mixture was stirred for 6 hours. The layers were separated, and the organic layer evaporated. The residue was taken up in 400 ml of dichloromethane, 250 ml of 2N aqueous sodium hydroxide was added, and the resulting two phase mixture was stirred rapidly overnight. The organic layer was separated and 100 ml of dimethylformamide were added. The solution was dried over sodium sulfate, filtered, and evaporated to give a yellow solid. Crystallization of the crude intermediate from ethyl acetate/toluene gave 1-(4-fluorophenyl)-2-(4-methylthiophenyl)ethan-1-one as white plates (25.8 g). Concentration of the filtrate followed by trituration of the residue gave an additional 15.7 g of white crystals.

Provenance & Evidence