反应详情

A suspension of 4-bromo-5-fluoro-2-methyl-7-nitro-2,3-dihydro-1H-isoindol-1-one (Compound 31E, 490 mg, 1.70 mmol) in EtOH (10.0 mL) was charged with iron powder (473 mg, 8.48 mmol) and then heated to reflux. After 10 min of reflux, the reaction mixture was charged with 1 M of HCl in H2O (2.03 mL, 2.03 mmol) and stirred at reflux for 10 min. The reaction mixture was filtered through a pad of celite. The filtrate was concentrated under reduced pressure. The residue was quenched with NaHCO3 (10 mL) and extracted with DCM (15 mL). The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to an orange solid. The crude material was purified using a Teledyne ISCO Combiflash® Rf system using DCM/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and then concentrated under reduced pressure to yield a bright yellow solid (218 mg, 50%). 1H NMR (CDCl3, 400 MHz): δ 6.38 (d, J=10.9 Hz, 1H) 5.29 (br. s., 2H) 4.22 (s, 2H) 3.14 (s, 3H). MS (ESI): m/z=260.99 [M+H]+. UPLC: tR=1.26 min (UPLC-TOF: polar—3 min).

1. temperatureheated to reflux
2. temperatureAfter 10 min of reflux
3. temperatureat reflux for 10 min
4. filtrationThe reaction mixture was filtered through a pad of celite
5. concentrationThe filtrate was concentrated under reduced pressure
6. customThe residue was quenched with NaHCO3 (10 mL)
7. extractionextracted with DCM (15 mL)
8. washThe organic layer was washed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure to an orange solid
12. customThe crude material was purified
13. additionThe fractions containing product
14. concentrationconcentrated under reduced pressure