Acetophenone → Ethyl 3-(3-fluorophenyl)-3-oxopropanoate

Participants

Reaction Conditions

Reaction Steps

Into a three-neck 2 L round-bottom flask equipped with an addition funnel, nitrogen inlet, magnetic stirrer, heating mantle, thermocouple and condenser, was placed 21.7 g (0.543 moles) of a 60%-in-oil dispersion of sodium hydride. To this was added 1 L dry hexane and the resulting suspension was stirred for 15 minutes. Stirring was halted and the solids were allowed to settle and the clear supernatant containing the hexane and dissolved oil was then removed via a cannula. Diethyl carbonate (1 L) was added to the solids and the suspension was heated to 120° C. To the hot suspension was cautiously added dropwise, over 40 minutes, a solution of 100 g (0.494 moles) of m-fluoro acetophenone dissolved in 250 mL of diethyl carbonate. As addition proceeded a reaction initiated, hydrogen was evolved and the color changed to tan. After the acetophenone-derivative addition was complete, the reaction was heated for 1 additional hour. The reaction mixture was cooled and was poured into a 2 L separatory funnel. The diethyl carbonate layer was twice washed with 10% acetic acid solution, dried over MgSO4 and filtered. The product was purified by vacuum distillation (bp 114-117° C. at 0.8-0.9 mm Hg) in 91% yield.

Provenance & Evidence