Acetic Acid → (5-Dimethylaminomethyl-2-methyl-benzofuran-3-yl)-acetic acid ethyl ester

Participants

Reaction Steps

To a solution of (5-formyl-2-methyl-benzofuran-3-yl)-acetic acid ethyl ester (1.00 g, 4.06 mmol) in anhydrous ethanol (25 mL) is added a 5 M solution of dimethylamine in ethanol (4.1 mL). The resulting reaction mixture is stirred for 18 h at room temperature. Acetic acid (1.4 mL) and NaBH3CN (279 mg, 4.22 mmol) are added and the resulting reaction mixture is heated at 50° C. for 4 h. After cooling to room temperature the solvents are removed by rotary evaporation. The residue is taken up in water, basified (pH=8) with a saturated aqueous NaHCO3 solution and extracted twice with EtOAc. The combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. The crude product is purified by flash column chromatography (silica gel, gradient of dichloromethane/methanol 10:0 to 9:1) to afford the title compound as a colorless oil (744 mg, 2.70 mmol, 67%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.39 (s, 1H), 7.31 (d, J=8.3 Hz, 1H), 7.15 (d, J=8.3 Hz, 1H), 4.14 (q, J=7.1 Hz, 2H), 3.58 (s, 2H), 3.50 (s, 2H), 2.41 (s, 3H), 2.25 (s, 6H), 1.23 (t, J=7.1 Hz, 3H). MS (ES+): 276 (M(C16H21NO3)+H)+.

Provenance & Evidence