Methyl iodide → 8-Bromo-2-chloro-3-methylquinoline

Temperature

0 °C

nBuLi (1.86 M in hexanes; 6.10 mL, 11.34 mmol) was added to a solution of diisopropylamine (1.600 mL, 11.34 mmol) in THF (20 mL) at 78° C., and the resulting solution was warmed to 0° C., stirred for 5 min, then cooled to 78° C. After 5 min, a solution of 8-bromo-2-chloroquinoline (Biofine International, Vancouver, BC; 2.5 g, 10.31 mmol) in THF (20.0 mL) was added (dropwise over 10 min) The resulting solution was stirred at 78° C. for 50 min and added (dropwise over 10 min) to a solution of MeI (1.925 mL, 30.9 mmol) in THF (20.0 mL) at 78° C. The resulting solution was stirred at 78° C. for 1 h. The mixture was then transferred to an ice bath, and water (1 mL) was added. The resulting mixture was warmed to RT and concentrated onto silica gel. Chromatographic purification (silica gel, 0-25% EtOAc/hexanes) furnished 8-bromo-2-chloro-3-methylquinoline (104b; 1.73 g, 6.74 mmol, 65% yield) as a light-yellow solid (64% pure), which was used without further purification in the subsequent step: m/z (ESI, +ve) 255.9 (M+H)+.

1. temperaturecooled to 78° C
2. waitAfter 5 min
3. stirringwas stirred at 78° C. for 50 min
4. stirringThe resulting solution was stirred at 78° C. for 1 h
5. customThe mixture was then transferred to an ice bath
6. temperatureThe resulting mixture was warmed to RT
7. concentrationconcentrated onto silica gel
8. customChromatographic purification (silica gel, 0-25% EtOAc/hexanes)

ORD record

ord-3a41c558e9d2432ca25c006f0b584316

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394297B2