Dimethyl Succinate → 2-[1-(4-fluoro-phenyl)-meth-(E)-ylidene]-succinic acid

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Reaction Steps

A solution of 4-fluorobenzaldehyde (1.0 g, 8.05 mmol) and dimethylsuccinate (1.41 g, 9.66 mmol) in tert-butanol (2 mL) was added drop-wise within 30 minutes to a refluxing mixture of potassium tert-butoxide (0.994 g, 8.86 mmol) in tert-butanol (8 mL). Refluxing was continued until all the starting material was consumed as demonstrated by TLC analysis. The reaction temperature was warmed to room temperature, and tert-butanol was removed in vacuo. The residue was dissolved in 1.0 N aqueous HCl (10 mL) and was extracted with ethyl acetate (2×5 mL). The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to obtain an oil. This crude product was dissolved in methanol (10 mL). An aqueous solution of 2.0 N NaOH (10 mL) was added into the solution at room temperature and the mixture was refluxed overnight. The resulting suspension was concentrated, and the obtained residue was dissolved in water (10 mL). The resulting solution was washed with ethyl acetate (2×10 mL). The aqueous layer was acidified (pH˜2) with the drop wise addition of concentrated HCl. The resulting mixture was extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to obtain a crude residue. Crystallization from ether/hexane gave 2-[1-(4-fluoro-phenyl)-meth-(E)-ylidene]-succinic acid (0.74 g, 41%) as a white solid. MS cald. for C11H8FO4 [(M−H)−]: 223, obsd. 223.1.

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