Ethanone, 1-(2,3-dihydro-6-benzofuranyl)- (9CI) synthesis

Yield:374706-07-7 73.7%

Reaction Conditions:

with bis-triphenylphosphine-palladium(II) chloride in toluene at 90; for 16 h;

Steps:

7.1 1-(2,3-dihydrobenzofuran-6-yl)ethan-1-one

The title compound was prepared according to procedures reported in the literature and known by persons skill in the art, using 6-bromo-2,3-dihydro-1-benzofuran (1 g, 5.03 mmol) as starting material. In a preferred method, 6-bromo-2,3-dihydro-1-benzofuran (1 g, 5.03 mmol) in toluene (10 mL) was degassed for 30 min. To this solution, 1-ethoxyvinyl tributyltin (2.012 g, 5.53 mmol) and bis(triphenylphosphine)palladium dichloride (0.35 g, 0.50 mmol) were added at rt and stirred for 16 hours at 90 °C. The reaction mixture was cooled to rt and filtered through celite. After evaporation of the solvent, 6 N HCl solution in water (10 mL) was added and the mixture was stirred for 1 hour at rt. It was concentrated and neutralized with sat. NaHCO₃. The desired product was extracted with DCM (50 mL), dried over Na₂SO₄ and concentrated. The crude product was purified by flash chromatography to give the title compound. Yield: 73.7% (0.6 g, pale yellow solid). ¹H NMR (400 MHz, DMSO-d₆): δ 7.48 (d, J = 7.64 Hz, 1H), 7.37-7.35 (d, J = 7.68 Hz, 1H), 7.26 (s, 1H), 4.58 (t, J = 8.76 Hz, 2H), 3.24 (t, J = 8.76 Hz, 2H), 2.53 (s, 3H). LCMS: (Method A) 163.2 (M+H), Rt. 3.01 min, 97.60% (Max).

References:

WO2017/144635,2017,A1 Location in patent:Page/Page column 32; 33