Hydrochloric Acid → 3-Fluoro-4-[(1E,3E)-5-oxo-1,3-pentadienyl]benzonitrile

Butyllithium (hexane solution, 1.53 N, 0.5 ml, 0.77 mmol) was added dropwise to a solution of diethyl 4-cyano-2-fluorobenzylphosphonate (209 mg, 0.77 mmol) obtained from Reference example 1-(1) in anhydrous tetrahydrofuran (4 ml) at −78° C. with stirring. The mixture was stirred at −78° C. for 30 minutes. At the end of this time, commercially available fumaraldehyde mono-dimethylacetal (100 mg, 0.77 mmol) in anhydrous tetrahydrofuran (2 ml) was added to the mixture, and the resulting mixture was stirred at −78° C. for 2 hours. The cooling bath was then removed and the mixture was stirred in an ice bath for a further 15 minutes. 0.1N hydrochloric acid (3.9 ml, 0.39 mmol) was added to the reaction mixture and the mixture was then stirred for 30 minutes in the ice bath and then for 1 hour at ambient temperature. At the end of this time, a saturated aqueous sodium hydrogen carbonate solution was added to the mixture in an ice bath. The resulting mixture was partitioned between ethyl acetate and water, the organic layer was washed with water and with aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then the solvent was distilled off under reduced pressure. The crystalline residue thus obtained was recrystallized from a mixture of ethyl acetate and hexane to afford the title compound (127 mg, 82% yield) as pale yellow crystals. m.p. 174-177° C.

1. stirringThe mixture was stirred at −78° C. for 30 minutes
2. stirringthe resulting mixture was stirred at −78° C. for 2 hours
3. customThe cooling bath was then removed
4. stirringthe mixture was stirred in an ice bath for a further 15 minutes
5. customThe resulting mixture was partitioned between ethyl acetate and water
6. washthe organic layer was washed with water and with aqueous sodium chloride solution
7. dry with materialdried over anhydrous magnesium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. customThe crystalline residue thus obtained
10. customwas recrystallized from a mixture of ethyl acetate and hexane

ORD record

ord-ace83d5a60b54ae1a5e0324f227d1e69

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07230023B2