Stannous chloride dihydrate → 5-Bromo-2-fluoro-4-methylaniline

To a stirred solution of 1-bromo-4-fluoro-2-methyl-5-nitrobenzene (18.0 g) in ethanol (300 mL) was added SnCl2.2H2O (51.8 g, 0.230 mol) at room temperature. The mixture was heated at reflux for 3 h. The solvent was evaporated under reduced pressure to give a residue, which was poured into ice water. The aqueous phase was basified with sat. NaHCO3 to pH 7. The solid was filtered off and the filtrate was extracted with dichloromethane (200 mL×3). The combined organics were dried over anhydrous Na2SO4 and evaporated under reduced pressure. The residue was purified by column chromatography (petroleum ether/EtOAc=10/1) to afford 5-bromo-2-fluoro-4-methylaniline (5.0 g, 30% yield for two steps). 1H NMR (400 MHz, CDCl3) δ 6.96 (d, J=8.8 Hz, 1H), 6.86 (d, J=11.6 Hz, 1H), 3.64 (br, 2H), 2.26 (s, 3H). MS (ESI) m/z (M+H+) 204.0.

1. temperatureThe mixture was heated
2. temperatureat reflux for 3 h
3. customThe solvent was evaporated under reduced pressure
4. customto give a residue, which
5. filtrationThe solid was filtered off
6. extractionthe filtrate was extracted with dichloromethane (200 mL×3)
7. dry with materialThe combined organics were dried over anhydrous Na2SO4
8. customevaporated under reduced pressure
9. customThe residue was purified by column chromatography (petroleum ether/EtOAc=10/1)

ORD record

ord-19513205f7cb4b1292693125f4cd789d

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846753B2