3,5-Dimethylaniline → 4-Bromo-3,5-dimethylaniline

Temperature

-78 °C

To a solution of 3,5-dimethyl-phenylamine (400 mg) in THF (35 mL) was added n-BuLi (1.45 mL, 2.5 M solution in hexane) at −78° C. The mixture was stirred at −78° C. for 20 min, allowed to warm up to −40° C. for 5 min, and then was cooled down to −78° C. again. After 10 min, B(OMe)3 (0.4 mL) was added dropwise. The mixture was stirred at −78° C. for 2.5 h, warmed up to 10° C. slowly, and then was cooled down to −78° C. again. Bromine (0.185 mL) was added dropwise to the mixture. The mixture was stirred at −78° C. for 1.5 h, and allowed to warm up to 0° C. for 1 h. The reaction was quenched with saturated NaHCO3 aqueous solution and 20% Na2S2O3 aqueous solution. The aqueous layer was extracted with EtOAc, and the organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, EtOAc:Hexane=5:95 to 40:60) to give 4-bromo-3,5-dimethyl-phenylamine as a white solid: MS (m/z) 200 (M+1); 1H NMR (CDCl3, 400 MHz) δ 6.43 (s, 2H), 3.52 (s, 2H), 2.31 (s, 6H).

1. temperatureto warm up to −40° C. for 5 min
2. temperaturewas cooled down to −78° C. again
3. waitAfter 10 min
4. stirringThe mixture was stirred at −78° C. for 2.5 h
5. temperaturewarmed up to 10° C. slowly
6. temperaturewas cooled down to −78° C. again
7. stirringThe mixture was stirred at −78° C. for 1.5 h
8. temperatureto warm up to 0° C. for 1 h
9. customThe reaction was quenched with saturated NaHCO3 aqueous solution and 20% Na2S2O3 aqueous solution
10. extractionThe aqueous layer was extracted with EtOAc
11. washthe organic extracts were washed with brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe crude product was purified by column chromatography (SiO2, EtOAc:Hexane=5:95 to 40:60)

ORD record

ord-07327bdba6544c6389747815e9275eba

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08222248B2