Diethyl Carbonate → Ethyl 3-(4-Fluorophenyl)-3-Oxopropanoate

Participants

Reaction Conditions

Reaction Steps

A solution of 4-fluoroacetophenone (100 g, 7.239 mol) in dry THF (100 ml) was added dropwise over 2.5 hours to a refluxing slurry of hexane-washed NaH (68.3 g, 60% oil dispersion, 1.708 mol) and diethyl carbonate (176.0 ml, 1.453 mol) in dry THF (300 ml). This solution was refluxed an additional 0.5 hours, cooled (0° C.), and a solution of ethanol (50 ml) in dry THF (150 ml) was added to quench the excess NaH. 300 ml of water and 100 ml of acetic acid were added, and this mixture was extracted with ethyl acetate (3×300 ml). The combined organics were washed with saturated NaHCO3 (1×500 ml), washed with brine (2×500 ml), dried (MgSO4), concentrated under reduced pressure, and distilled at 10 mm to yield 146.3 g of the title compound.

Provenance & Evidence