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

Participants

Reaction Conditions

Reaction Steps

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)+.

Provenance & Evidence