5-Bromo-1-methyl-1H-imidazole → HCID 86716088, compound

Participants

Reaction Steps

A solution of 5-bromo-1-methyl-1H-imidazole (95.7 mg, 0.594 mmol) in DCM (0.6 mL) was stirred on an ice bath while iPrMgCl—LiCl (0.495 mL, 1.2 M in THF, 0.593 mmol) was added dropwise over 2.5 min under argon. After 15 min stirring at room temperature, the Grignard solution was added dropwise over 2.5 min to a slurry of 2,4-dichloro-8-fluoro-3-phenylquinoline-6-carbaldehyde (140 mg, 0.436 mmol, Intermediate 46, step b) in LaCl3-2LiCl (0.779 mL, 0.56 M in THF, 0.436 mmol) on an ice bath. The red-colored reaction was removed from the ice bath immediately following Grignard addition, and after 15 min stirring under ambient conditions, the reaction was partitioned with DCM (5 mL) and 1M NaHCO3 (0.6 mL). The mixture was filtered and the filter cake washed with 3 mL DCM. The combined clear yellow filtrates were dried (Na2SO4), filtered, and concentrated, and the crude secondary alcohol was dissolved in DCM (2 mL), treated with MnO2 (379 mg, 4.36 mmol), and stirred at 40° C. for 2 hours. The reaction was then diluted with DCM (4 mL) and filtered, and the clear yellow filtrate was concentrated and flash chromatographed with a 5% acetone/heptane to 100% acetone gradient to yield the title compound as a white solid.

Provenance & Evidence