1,2-Difluorobenzene → (S)-N-trifluoroacetyl-2-amino-4-oxo-4-(3',4'-difluorophenyl) Butanoic Acid

Participants

Reaction Steps

To an ice-cooled solution of 1,2-difluorobenzene (25 ml; 0.256 mol) in dry dichloromethane (170 ml), (S)-N-trifluoroacetylaspartic anhydride (12 g.; 0.054 mol) was added in one portion. To the resulting solution, anhydrous aluminium trichloride (21.5 g; 0.16 mol.) was slowly added portionwise, under vigorous stirring and dry nitrogen atmosphere, maintaining the temperature below 10° C. The so obtained deep-yellow suspension was stirred at room temperature for 3 hrs. and then at 50° C. for 5 hrs. The resulting reaction mixture was then poured into ice (400 g), and extracted with dichlorometane (3×100 ml), the collected organic extracts were washed with brine (2×50 ml ), dried (Na2SO4), and evaporated in vacuum to afford the crude product (7.3 g) as an oily material. Recrystallisation from hexane/ethyl ether afforded the pure titled compound as colourless prisms (8 g; 47%), m.p. 136°-137° C.

Provenance & Evidence