反应详情

To a suspension of sodium hydride (60% in paraffin oil, 31g, 686 mmol) in toluene (150 mL) was added a solution of 4-fluorobenzaldehyde (30 g, 214 mmol) and dimethyl methylsuccinate (58 g, 312 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, 214 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 (28g, 27.5% overall). MS cald. for C12H12FO4 [(M+H)+]: 239, obsd. 239.2.

1. customThe reaction was quenched by slow addition of 2.0 N aqueous NaOH (300 mL) at 0° C
2. stirringThe resulting mixture was stirred at 110° C. for 4 hours
3. temperatureThe mixture was then cooled to room temperature
4. additionthe aqueous layer was diluted with water (300 mL)
5. washwashed with Et2O (2×300 mL)
6. temperatureThe aqueous phase was cooled in an ice-water bath
7. additionAddition of concentrated HCl
8. extractionwas followed by extraction with ethyl acetate (2×100 mL)
9. washThe combined organic extracts were washed with water (50 mL)
10. dry with materialThe organic phase was dried over anhydrous sodium sulfate
11. concentrationconcentrated
12. customThe residue was crystallized from ethyl acetate-hexanes