Hydrochloric Acid → 1-(3-Fluorophenyl)-2-(4-methylthiophenyl)ethanone

Participants

Reaction Conditions

Reaction Steps

A solution of the intermediate from Step 1 (3.57 g, 12.4 mmol) and triethylamine (1.41 g, 13.9 mmol) dissolved in 35 mL of anhydrous toluene was cooled to 0° C. and treated with diphenylphosphoryl azide (3.53 g, 12.8 mmol). The solution was maintained at 0° C. for twenty minutes and warmed to room temperature for 3 hours. The reaction was poured into water, extracted with ether, dried over magnesium sulfate, and concentrated in vacuo to remove the ether. The remaining toluene solution was heated to reflux for 1 hour. tert-Butyl alcohol (4 mL, 42 mmol) was added to the reaction mixture. After an additional twenty minutes, concentrated hydrochloric acid (4 mL) was cautiously added and the reaction maintained at 80° C. overnight (14 hours). After cooling the solution to room temperature, the mixture was poured into a separatory funnel and washed with water. The toluene layer was dried with anhydrous MgSO4, filtered and concentrated in vacuo to give a yellow powder. The crude solid was crystallized from a mixture of dichloromethane and isooctane to provide 1.30 g (40%) of the desired ketone: mp 116°-120° C. 1H NMR (CDCl3) 300 MHz 7.77 (d, J=7.9 Hz, 1H), 7.68 (dt, J=9.4 Hz 2.6 Hz, 1H), 7.43 (m, 1H), 7.21-7.29 (m, 3H), 7.18 (d, J=8.3 Hz, 2H), 4.22 (s, 2H), 2.46 (s, 3H); 19F NMR (CDCl3) -111.82 (m). Mass spectrum M+H=261.

Provenance & Evidence