Water → Butanedioic acid, 2-methylene-, methyl ester

Temperature

70 °C

Potassium t-butoxide (68.8 g) was weighed into a reaction flask equipped with a mechanical stirrer, placed under a nitrogen atmosphere and 700 mL of toluene was added followed by 4,4′-difluorobenzophenone (100 g). The reaction mixture was stirred mechanically and heated to 70° C. A solution of dimethyl succinate (80 g) in 100 mL of toluene was added to the reaction mixture over a 60 minute period. The reaction mixture was heated at 70° C. for 4 hours. After cooling to room temperature, the reaction mixture was poured into 500 mL of water and the toluene layer discarded. The aqueous layer was extracted with diethyl ether (1×400 mL) to remove the neutral products, and then acidified the aqueous layer with concentrated HCl. A brownish-yellow oily solid was obtained from the aqueous layer, and was extracted with 3×300 mL of ethyl acetate. The organic layers were combined, washed with saturated NaCl solution (1×500 mL) and dried over anhydrous sodium sulfate. Removal of the solvent by rotary evaporation yielded 122 g of 4,4-di(4-fluorophenyl))-3-methoxycarbonyl-3-butenoic acid as a brownish oily solid. This material was not purified further but was used directly in the next step.

1. customequipped with a mechanical stirrer
2. temperatureThe reaction mixture was heated at 70° C. for 4 hours
3. temperatureAfter cooling to room temperature
4. extractionThe aqueous layer was extracted with diethyl ether (1×400 mL)
5. customto remove the neutral products
6. customA brownish-yellow oily solid was obtained from the aqueous layer
7. extractionwas extracted with 3×300 mL of ethyl acetate
8. washwashed with saturated NaCl solution (1×500 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. customRemoval of the solvent
11. customby rotary evaporation

ORD record

ord-4ca55afa719f4b9788b2d1b692eccdeb

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07527754B2