Chlorotrimethylsilane → 2-(4-Bromo-2-chlorophenyl)ethanamine

To a stirred suspension of LiBH4 (2.0 M, 73 mL, 145 mmol) in THF (60 mL) at room temperature was added chlorotrimethylsilane (32 g, 290 mmol), dropwise over 10 min. After stirring at room temperature for 20 min, nitrogen gas was bubbled through the mixture for 5 min to remove the remaining trimethylsilane that had formed. A solution of 4-bromo-2-chloro-1-(2-nitrovinyl)benzene (9.5 g, 36.2 mmol) in THF (60 mL) was added dropwise over 10 min with stirring at room temperature. The resulting mixture was heated at reflux for 1 h. The reaction mixture was cooled in an ice bath and carefully quenched with MeOH (100 mL). The solvent was evaporated and the residue was partitioned between 20% KOH (120 mL) and CH2Cl2 (60 mL). The organic layer was dried, concentrated, purified by column chromatography (silica, ethyl acetate/hexanes gradient) to obtain the desired product (8.5 g, 95%) as a light yellow oil: ESI MS m/z 234 [C8H9BrClN+H]+.

1. customnitrogen gas was bubbled through the mixture for 5 min
2. customto remove the remaining trimethylsilane that
3. customhad formed
4. stirringwith stirring at room temperature
5. temperatureThe resulting mixture was heated
6. temperatureat reflux for 1 h
7. temperatureThe reaction mixture was cooled in an ice bath
8. customcarefully quenched with MeOH (100 mL)
9. customThe solvent was evaporated
10. customthe residue was partitioned between 20% KOH (120 mL) and CH2Cl2 (60 mL)
11. customThe organic layer was dried
12. concentrationconcentrated
13. custompurified by column chromatography (silica, ethyl acetate/hexanes gradient)

ORD record

ord-eb5c22c3b3df40bab19b360dc6367249

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962648B2