Thionyl Chloride → 1-Benzyl-3,3-difluoropyrrolidine-2,5-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of the crude 4-(benzylamino)-3,3-difluoro-4-oxobutanoic acid in iPrOAc (40 mL), SOCl2 (2.04 mL, 27.9 mmol, 2 eq) was added at ambient temperature. The reaction solution was stirred at 55° C. for 4 hr. The reaction was cooled to 0-5° C. Half saturated brine (50 mL) was added slowly to quench the excess SOCl2. The organic phase was washed with brine (70 mL) and 2 M Na2CO3 (about 50 mL) to pH=8-9, extracted two times with EtOAc. The combined organic layer was washed with brine (50 mL), the organic phase was dried over MgSO4, filtered and concentrated. The crude residue was diluted with CH2Cl2 and filtered to remove precipitate. The concentrated filtrate was purified by column chromatography and eluted with 2-20% EtOAc/Heptane to obtain the title compound as a clear oil (1.74 g, 65%)1H NMR (400 MHz, CDCl3) δ ppm 7.30-7.43 (m, 5 H) 4.76 (s, 2 H) 3.18 (t, J=12.53 Hz, 2 H).

Provenance & Evidence