反应详情

To a solution of pyrrolidin-2-one (9.38 mL, 121 mmol) in N,N-dimethylformamide (DMF) (200 mL) was added in portions sodium hydride (6.04 g, 151 mmol) (60%/mineral oil) in 10 min and the mixture was stirred under nitrogen atmosphere at ambient temperature for 2 h then 1-(bromomethyl)-2,3-difluorobenzene (15.37 mL, 121 mmol) was added dropwise over 15 min and the mixture was stirred at ambient temperature for 2.5 h. Water (600 mL) was added and the mixture was stirred at ambient temperature for 30 min then extracted with EtOAc. The organic phase was washed with water (3×), and brine, dried (Na2SO4), concentrated, dissolved in acetonitrile and washed with hexanes (2×). The acetonitrile phase was concentrated, dried in vacuo to provide 1-(2,3-difluorobenzyl)pyrrolidin-2-one (19.14 g, 86 mmol, 71.2% yield) as a yellowish oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.03 (quint, J=7.61 Hz, 2 H), 2.43 (t, J=8.10 Hz, 2 H), 3.34 (t, J=7.02 Hz, 2 H), 4.54 (s, 2 H), 6.99-7.17 (m, 3 H); LCMS (m/z) ES+=212 (M+1).

1. stirringthe mixture was stirred at ambient temperature for 2.5 h
2. stirringthe mixture was stirred at ambient temperature for 30 min
3. extractionthen extracted with EtOAc
4. washThe organic phase was washed with water (3×), and brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated
7. dissolutiondissolved in acetonitrile
8. washwashed with hexanes (2×)
9. concentrationThe acetonitrile phase was concentrated
10. customdried in vacuo