3-(4-Chloro-phenyl)-3-oxo-propionic acid ethyl ester can be prepared from 4-chlorobenzoic acid.
To a solution of 4-chlorobenzoic acid (30.0 g, 0.192 mol) in DCM (250 mL) was added oxalyl chloride (25 mL, 0.288 mol) and then DMF (0.5 mL) was added dropwise. The reaction mixture was refluxed for 2 hours. The clarified yellow solution obtained was concentrated under vacuum to obtain the acyl chloride as a yellow liquid. TEA (67 mL) was added to a solution of potassium ethyl malonate (41 g, 0.241 mol) in acetonitrile (537 mL). After cooling in an ice-salt bath, MgCl2 (27.4 g, 0.288 mol) was added and the resulting mixture was stirred at this temperature for 3 hours. Acyl chloride (prepared as described above) was added and the reaction mixture was warmed to ambient temperature and stirred overnight. The mixture was cooled in an ice bath and 2N HCl (600 mL) was carefully added. The mixture was stirred in an ice bath for 1.5 hours and then transferred to a split funnel and extracted with ethyl acetate (3 x 200 mL). The combined organic layers were washed with saturated sodium bicarbonate (450 mL), brine (250 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford the crude product ethyl 3-(4-chlorophenyl)-3-oxo-propionate (48.6 g), which was used without purification.
