Methyl iodide → 2-[Methyl-(5,6,7,8-tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

Participants

Reaction Steps

To a solution of NaH (sodium hydride, 60% dispersion, 124 mg, 3.08 mmol) in anhydrous THF (20 mL) is added dropwise the solution of 2-[(5,6,7,8-tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester (37) (280 mg, 0.77 mmol) in THF (5 mL) at 0° C. After stirring for 20 min, methyl iodide (377 μL, 6.05 mmol) is added dropwise and the resulting suspension is warmed up to RT and continued stirring overnight. After being quenched by saturated ammonium chloride aqueous solution (5 mL), the reaction mixture is diluted in EtOAc (50 mL). The organic layer is separated, washed with water (1×5 mL) and brine (2×5 mL), dried over anhydrous Na2SO4 and concentrated in in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 0%-30% EtOAc in heptane) to give a pure product (120) as a colorless semisolid (250 mg, 86%).

Provenance & Evidence