2-Methylpyridine → 6-bromo-3-(1-hydroxy-2-pyridin-2-ylethyl)-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-one

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Reaction Conditions

Reaction Steps

Under a nitrogen stream, a solution (1.61M, 15.8 ml) of n-butyllithium in hexane was added to THF (15 ml) at −50° C. or below, and a solution (2.5 ml) of 2-methylpyridine (2.5 g) in THF was added dropwise at −50° C. or below. The reaction mixture was allowed to warm to −20° C. and stirred for 10 min. and then cooled to −50° C. and magnesium bromide (2.5 g) was added. The reaction mixture was allowed to warm to room temperature, stirred for 30 min. and bromo(pyridin-2-ylmethyl)magnesium was prepared. The obtained suspension (4 ml) of bromo(pyridin-2-ylmethyl)magnesium was added to a solution of 6-bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbaldehyde (500 mg) in THF (5 ml), and the mixture was stirred at room temperature for 10 min. To the reaction mixture were added water and saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (ethyl acetate) to give the title compound (400 mg).

Provenance & Evidence