Diisopropylamine → 2-(3'-Dimethylaminobenzoylmethyl)nicotinic acid N-methylamide

Participants

Reaction Steps

263 ml. of 1.6 M.n-butyl lithium in hexane (420 mmol.) were slowly added to a solution of 58.7 ml. (420 mmol.) of diisopropylamine in 200 ml. of dry tetrahydrofuran stirred at -10° C. under nitrogen. To the resulting solution of lithium diisopropylamide, a solution of 30 g. (200 mmol.) of 2-methylnicotinic acid N-methylamide (Compound XII) in 200 ml. of dry tetrahydrofuran was slowly added at -20°--30° C. The resulting red reaction mixture was stirred under nitrogen at -20°--30° C. for an additional two hours. Then, a solution of 38.6 g. (200 mmol.) of ethyl 3-dimethylaminobenzoate in 100 ml. of dry tetrahydrofuran was slowly added at -20°--30° C. with stirring under nitrogen. Stirring under nitrogen was continued for 1 hour at the same temperature. The reaction mixture was then quenched with 250 ml. of saturated sodium chloride solution and extracted three times with ethyl acetate. The ethyl acetate phases were combined, washed four times with water, once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered and evaporated at reduced pressure to a thick oil (55.6 g.) which was dissolved in a small amount of isopropanol and chromatographed on silica gel using 5% isopropanol/chloroform as the eluant. The last major fraction to be eluted (approx. 24 g.) was rechromatographed on silic gel using 2% isopropanol/chloroform as the eluant. The largest fraction contained the crude product (17.2 g.).

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