5-Bromo-2-methylpyridine → HCID 86716091, compound

Participants

Reaction Steps

A solution of 5-bromo-2-methylpyridine (380 mg, 2.21 mmol) in DCM (2.2 mL) was stirred on an ice bath while iPrMgCl—LiCl (1.84 mL, 1.2 M in THF, 2.21 mmol) was added dropwise over 1-2 min under argon. After 30 min stirring at room temperature, the dark brown Grignard solution was added dropwise over 1-2 min to a slurry of 2,4-dichloro-8-methyl-3-phenylquinoline-6-carbaldehyde (460 mg, 1.46 mmol, Intermediate 47, step b) in LaCl3-2LiCl (2.60 mL, 0.56 M in THF, 1.46 mmol) on an ice bath under argon. The homogeneous reddish-amber reaction was removed from the ice bath immediately following Grignard addition and stirred at room temperature overnight. The resulting homogeneous brown amber solution was diluted with 9:1 DCM/MeOH (14 mL) and 5 M NH4Cl (0.72 mL), shaken with Celite® and filtered, and the filter cake was washed with 9:1 DCM/MeOH (1×5 mL). The combined clear amber filtrates were dried (Na2SO4), filtered, and concentrated repeatedly from DCM. The residue was taken up in DCM (15 mL) and the resulting slurry was stirred with MnO2 (1.27 g, 14.5 mmol) under air (capped) at 40° C. for 32 hours. The reaction was diluted with 9:1 DCM/MeOH (10 mL) and Celite®, and filtered on a bed of Celite®. The filtrate was concentrated and flash chromatographed with a DCM to 30% EtOAc/DCM gradient to provide the title compound as a colorless film.

Provenance & Evidence