Iodine → HCID 86701271, compound

Participants

Reaction Conditions

Reaction Steps

To an oven-dried flask containing a magnetic stir bar was added freshly ground zinc dust (149 mg, 2.28 mmol) and a small volume of DMF (100 μL) was added to just cover the dust. Iodine (57 mg, 0.23 mmol) was added and the mixture stirred for 2 min and then warmed to 40° C. A solution of (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-8-(2-iodoethyl)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (200 mg, 0.38 mmol) in DMF (1 mL) was added slowly at 40° C. After 15 min, the reaction mixture was cooled to ambient temperature (about 22° C.), and a solution of Pd((o-tol)3P)2Cl2 (7.5 mg, 0.01 mmol) and 1-fluoro-4-iodobenzene (58 uL, 0.49 mmol) in DMF (900 μL) was added to the reaction and the reaction was warmed back to 40° C. and stirring continued for 2.5 h. The mixture was cooled, diluted with EtOAc (2 mL) and filtered through a 0.45 μm fritted filter disc. The filtrate was diluted with EtOAc (20 mL), washed with saturated NaHCO3 solution (15 mL), dried over Na2SO4, filtered, and concentrated. Purification by column chromatography (SiO2, hexanes/EtOAc gradient) gave the title compound (92 mg, 51%) as a white glassy solid: 1H NMR (300 MHz, CDCl3) δ 7.31-7.14 (m, 3H), 7.14-7.04 (m, 2H), 5.46-5.15 (m, 2H), 5.06 (t, J=9.9 Hz, 1H), 4.91-4.72 (m, 2H), 3.61 (s, 1H), 2.76-2.48 (m, 3H), 2.40 (dt, J=13.8, 8.2 Hz, 1H), 2.17-1.99 (m, 1H), 1.73-1.52 (m, 1H), 1.45 (s, 9H), 1.25 (d, J=6.3 Hz, 3H), 1.16 (d, J=7.0 Hz, 6H); ESIMS m/z 500 ([M+Na]+).

Provenance & Evidence