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

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.

1. temperatureRefluxing
2. customwas consumed
3. customtert-butanol was removed in vacuo
4. dissolutionThe residue was dissolved in 1.0 N aqueous HCl (10 mL)
5. extractionwas extracted with ethyl acetate (2×5 mL)
6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo
8. customto obtain an oil
9. temperaturethe mixture was refluxed overnight
10. concentrationThe resulting suspension was concentrated
11. dissolutionthe obtained residue was dissolved in water (10 mL)
12. washThe resulting solution was washed with ethyl acetate (2×10 mL)
13. additionwith the drop wise addition of concentrated HCl
14. extractionThe resulting mixture was extracted with ethyl acetate (3×10 mL)
15. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
16. concentrationconcentrated in vacuo
17. customto obtain a crude residue
18. customCrystallization from ether/hexane

ORD record

ord-3d18671b3c1c4fbdb5138f209c0bd28f

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691993B2