Methanol → 2-[1-(4-fluoro-phenyl)-meth-(E)-ylidene]-3-methyl succinic acid

Participants

Reaction Steps

To a suspension of sodium hydride (60% in paraffin oil, 31 g, 775 mmol) in toluene (150 mL) was added a solution of 4-fluorobenzaldehyde (30 g, 242 mmol) and dimethyl methylsuccinate (58 g, 362 mmol) in toluene (150 mL) over 1 hour at 0° C. under nitrogen. The reaction was initiated by addition of a drop of methanol at room temperature and was stirred at room temperature for 2 hours. The reaction was quenched by slow addition of 2.0 N aqueous NaOH (300 mL) at 0° C. The resulting mixture was stirred at 110° C. for 4 hours. The mixture was then cooled to room temperature and the aqueous layer was diluted with water (300 mL) and washed with Et2O (2×300 mL). The aqueous phase was cooled in an ice-water bath. Addition of concentrated HCl was followed by extraction with ethyl acetate (2×100 mL). The combined organic extracts were washed with water (50 mL) followed by brine (50 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was crystallized from ethyl acetate-hexanes to give 2-[1-(4-fluoro-phenyl)-meth-(E)-ylidene]-3-methyl succinic acid. The procedure above was repeated using a separate amount of 4-fluorobenzaldehyde (30 g, 242 mmol). The products of the two reactions were combined to provide 2-[1-(4-fluoro-phenyl)-meth-(E)-ylidene]-3-methyl succinic acid as a pale yellow solid (28 g, 24% overall). MS cald. for C12H12FO4 [(M+H)+] 239, obsd. 239.2.

Provenance & Evidence