Sodium hydride → Methyl 5-[3-(quinolin-2-ylmethoxy)-benzyloxy]-nicotinate

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Reaction Steps

To a solution of 5-hydroxy nicotinic acid methyl ester (200 mg, 1.3 mmol) in DMF (3 mL) is added 60% sodium hydride emulsion (50 mg, 1.2 mmol) and this mixture is stirred 30 minutes. The free base of 2-(3-chloromethyl-phenoxymethyl)-quinoline hydrochloride (350 mg, 1.2 mmol, example 49) is prepard by partioning the material between ethyl ether and sodium bicarbonate and drying the organic phase with magnesium sulfate. A solution of this free base in DMF (2 mL) is added to the alcohol and this mixture is stirred at 25° C. for 16 hours. The solvent is removed in vacuo, dichloromethane (10 mL) and water (5 mL) is added, and this mixture is acidified to pH6 with acetic acid. The organic layer is dried over magnesium sulfate and the solvent removed in vacuo. The residue is purified by flash chromatography (silica, 4% methanol in dichloromethane) to give the title compound. MS (ESI) 401 (M+H)+.

Provenance & Evidence