Benzoic acid, 3-methyl-, methyl ester → 2-(4-methylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one

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To a solution of diisopropylamine (1.2 mL, 8.56 mmol) in THF (15 mL) at 0° C. was added n-butyllithium (5.2 mL of a 1.6 M solution in hexane, 8.32 mmol). After stirring at 0° C. for 10 minutes the resulting lithium diisopropylamide solution was treated with a solution of 2-methyl-N-(4-methylbenzyl)benzamide (616 mg, 2.57 mmol) in THF (20 mL) over 15 min. The resulting deep brown-red solution was stirred at 0° C. for 55 minutes at which time it was treated with a solution of 3-methylbenzoic acid methyl ester (0.39 mL, 2.76 mmol) in THF (20 mL) over 20 minutes. After an additional 1 hour at 0° C. the reaction was quenched by the addition of 3N HCl (25 mL). The biphasic mixture was then heated to reflux with vigorous stirring. After 75 minutes at reflux the reaction mixture was allowed to cool to ambient temperature overnight. After cooling overnight, the reaction was concentrated to remove most of the THF. The resulting residue was diluted with ether (100 mL), and water (50 mL), and then basified by careful addition of solid Na2CO3. The basic aqueous was extracted with ether (3×40 mL), combined organics were washed with brine (50 mL), dried over Na2CO3, filtered, and concentrated to afford a yellow oil. The crude product was purified by silica gel column chromatography on a Jones Flashmaster instrument eluting with a gradient from 0% to 6% ethyl acetate/hexane on a 50 g silica column. The product peak was collected to afford 2-(4-methylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one (408 mg, 47% yield) as a yellow oil that slowly solidified to a waxy solid:

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