Pyridine → 7-Bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid methylamide

Participants

Reaction Steps

To a solution of 7-bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid (4.99 g, 18.41 mmol) in dry THF (40 mL) was added at room temperature thionychloride (2 mL, 27.61 mmol) and DMF (0.14 mL, 1.84 mmol). The reaction mixture was stirred 1 hr then methylamine hydrochloride (2.48 g, 36.82 mmol) was added followed by slow addition of pyridine (4.5 mL, 55.23 mmol). The reaction mixture was stirred overnight then water and ethyl acetate were added. The layers were separated. The aqueous layer was extracted twice with ethyl acetate. The combined extracts were washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (50% to 100% ethyl acetate in hexane, then 40% MeOH in Ethyl acetate) to give 1.17 g of 7-bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid methylamide (22%). 1H NMR (300 MHz; CDCl3): 1.36 (s, 6H), 2.99 (d, J=4.5 Hz, 3H), 4.39 (s, 2H), 6.25 (br s, 1H), 7.54 (d, J=1.5 Hz, 1H), 7.70 (d, J=1.5 Hz, 1H).

Provenance & Evidence