Stannous chloride dihydrate → 5-Bromo-6-fluoropyridin-3-amine

To a solution of 3-bromo-2-fluoro-5-nitropyridine from Step 126a above (5.0 g, 23 mmol) in MeOH (100 mL) was added tin(II) chloride dihydrate. The mixture was heated at reflux for 3 hours, then cooled to ambient temperature and concentrated in vacuo. The residue was diluted with saturated aqueous NaHCO3 and EtOAc resulting in formation of an emulsion which was filtered. The filtrate was poured into a separatory funnel and the layers were separated. The aqueous phase was extracted with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), and concentrated. Purification by chromatography (silica gel; hexane/EtOAc, 70:30) afforded 3.61 g (83%) of the title compound as a yellow solid: mp 91-92° C.; 1H NMR (CDCl3, 300 MHz) δ 7.15 (dd, J=2.5, 7.5 Hz, 1H), (dd, J=2.0, 2.5 Hz, 1H); MS (DCI/NH3) m/z 191, 193 (M+H)+ 208, 210 (M+NH4)+.

1. temperatureThe mixture was heated
2. temperatureat reflux for 3 hours
3. concentrationconcentrated in vacuo
4. additionThe residue was diluted with saturated aqueous NaHCO3 and EtOAc resulting in formation of an emulsion which
5. filtrationwas filtered
6. additionThe filtrate was poured into a separatory funnel
7. customthe layers were separated
8. extractionThe aqueous phase was extracted with EtOAc
9. washThe combined organic extracts were washed with brine
10. dry with materialdried (MgSO4)
11. concentrationconcentrated
12. customPurification by chromatography (silica gel; hexane/EtOAc, 70:30)

ORDレコード

ord-ec6cf76c85e84885b26729f43825cd00

出典データセット

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06133253