Diethyl Ether → 4-(Tert-butyl)-2-methylpyridine

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Reaction Steps

Cool a solution of methyl lithium in ether (200 mL, 1.6 M, 320.00 mmol) in an ice bath and add 4-tert-butyl-pyridine (20.28 g, 150.00 mmol) drop wise. Once the substrate is added, warm the reaction to ambient temperature for 3 hours. Concentrate the reaction to near dryness to remove the ether and then add anhydrous toluene (200 mL) and heat to reflux for 20-21 hours. Cool in an ice bath while slowly and cautiously adding ice to quench the reaction. Add water (200 mL) and then extract the aqueous with ethyl acetate (3×250 mL) and separate the layers. Pool, desiccate, filter and concentrate the organic extracts to an oil. Chromatograph the oil on silica using a gradient of 0→50% ethyl acetate hexanes over 25 minutes to yield the title compound (16.60 g, 111.23 mmol). MS(ESI), m/z 150 (M+1).

Provenance & Evidence