反应详情

To an Argon sparged solution of 1,3-dibromo-2-chloro-5-methylbenzene (5 g, 17.6 mmol), benzophenone imine (3.1 mL, 18.5 mmol), sodium tert-butoxide (2.53 g, 26.4 mmol) in toluene, (S)-BINAP (1.6 g, 2.6 mmol) and Pd2(dba)3 (0.81 g, 0.88 mmol) were added and the reaction was heated in an oil bath. When the temperature reached 60° C. an exotherm was noted, with reflux of the solvent. Heating was maintained and the reaction was complete after 1.5 hours. The reaction mixture was cooled, diluted with Et2O and stirred with Siliabond DMT (Pd scavenger), and was then filtered through Celite. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford a sticky brown residue. The residue was dissolved in THF (60 mL) and aqueous 6.0 M HCl solution was added. The reaction mixture was stirred for 30 minutes, partitioned with Et2O and 1M NaOH was added until the aqueous layer was pH 9. The layers were separated and the organic layer was washed with water, brine, dried (MgSO4), and concentrated. Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane) furnished 3-bromo-2-chloro-5-methylaniline (1.7 g) with a small amount of benzophenone as a contaminant: 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H) 4.11 (br s, 2H) 6.52 (s, 1H) 6.85 (s, 1H).

1. temperaturethe reaction was heated in an oil bath
2. customreached 60° C.
3. temperaturewith reflux of the solvent
4. temperatureHeating
5. temperaturewas maintained
6. temperatureThe reaction mixture was cooled
7. filtrationwas then filtered through Celite
8. washThe filtrate was washed with water, brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated
11. customto afford a sticky brown residue
12. custompartitioned with Et2O and 1M NaOH
13. additionwas added until the aqueous layer
14. customThe layers were separated
15. washthe organic layer was washed with water, brine
16. dry with materialdried (MgSO4)
17. concentrationconcentrated
18. customPurification by flash chromatography (SiO2, 0-20% EtOAc in heptane)