Dimethyl Sulfate → 3-Bromo-6-chloro-2-fluoro-N-methylbenzenamine

Temperature

60 °C

3-Bromo-6-chloro-2-fluoroaniline (1.2 g, 5.2 mmol) was dissolved in THF (12 mL) in a 100 mL round bottomed flask and treated with tetra-N-butyl ammonium bromide (0.015 g, 0.05 mmol) and powdered sodium hydroxide (0.83 g, 20.9 mmol) with stirring. After 5 minutes, the dark mixture was treated with dimethyl sulfate (1.3 g, 10.4 mmol) and the mixture heated at 60° C. for 2 hours. Analysis by TLC (hexanes: ethyl acetate/20:1) indicated some starting material remained. Added additional dimethyl sulfate (0.66 g, 5.2 mmol) and continued heating for 1.5 hour then stirred at room temperature overnight. The reaction was partitioned between diethyl ether and water and the layers separated and the aqueous phase extracted with ether. The combined ether layers were washed with water and dried (MgSO4). Filtration, concentration and purification by flash silica gel chromatography (hexanes) gave N-(3-bromo-6-chloro-2-fluorophenyl)-N-methylamine (0.81 g) as a colorless oil: 1H NMR (300 MHz, CDCl3): δ 6.93 (dd, 1H, J=8.4), 6.83 (dd, 1H), 4.00 (bs, 1H), 3.09 (d, 3H).

1. temperaturecontinued heating for 1.5 hour
2. stirringthen stirred at room temperature overnight
3. customThe reaction was partitioned between diethyl ether and water
4. customthe layers separated
5. extractionthe aqueous phase extracted with ether
6. washThe combined ether layers were washed with water
7. dry with materialdried (MgSO4)
8. filtrationFiltration, concentration and purification by flash silica gel chromatography (hexanes)

ORD record

ord-12148d6e30c54f8a94c4ae7ec124b1b0

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07314849B2