Tris(furan-2-yl)phosphane → 5-(3-(3-Hydroxy-propyl)-phenyl)-isoxazole-3-carboxylic Acid Ethyl Ester

Participants

Reaction Steps

To 3-(3-iodophenyl)-1-propanol (1.55 g, 5.60 mmol), tri-2-furylphosphine (130 mg, 0.56 mmol), tris(dibenzylideneacetone)dipalladium (256 mg, 0.23 mmol), and CuI (107 mg, 0.56 mmol) was added DMF (10 mL). To this mixture was added a solution of 5-tributylstannanyl-isoxazole-3-carboxylic acid ethyl ester (2.41 g, 5.60 mmol) as a solution in DMF (10 mL). The reaction was stirred under N2 at ambient temperature for 1 hour, then 5% (w/v) KF(aq) (100 mL) and diethyl ether (50 mL)were added. The biphasic mixture was stirred vigorously for 10 minutes, then filtered through diatomaceous earth to remove the solid precipitates. The precipitate was washed with diethyl ether to recover any organic material from the filter pad, then the combined filtrate and washings were separated. The aqueous layer was extracted with additional ether (2×25 ML), the combined ether layers were washed with water (1×25 mL), and brine (1×25 mL), dried over MgSO4, filtered, and concentrated to an oil. The product was purified via silica gel chromatography, eluting with 40% ethyl acetate/hexanes to provide the titled compound (950 mg, 2%). 1H NMR (500 MHz, d6-DMSO) δ 7.81 (s, 1H), 7.77 (d, 1H, J=7.5 Hz), 7.47 (t, 1H, J=7.6 Hz), 7.47 (s, 1H), 7.39 (d, 1H, J=7.4 Hz), 4.49 (t, 1H, J=5.2 Hz), 4.41 (q, 2H, J=7.2 Hz), 3.44 (q, 2H, J=5.9 Hz), 2.71 (t, 2H, J=7.8 Hz), 1.78 (m, 2H), 1.36 (t, 3H, J=7.2 Hz); MS (ESI) m/z 276 (M+H)+, 293 (M+NH4)+, 298 (M+Na)+.

Provenance & Evidence