Iodine → HCID 86701257, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of freshly ground zinc dust (139 mg, 2.13 mmol) in an oven-dried flask containing a stir bar were added DMF (200 μL; just covered the dust) and iodine (54 mg, 0.21 mmol), and the mixture was stirred for 1 min. To the mixture was added a solution of (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-8-(iodomethyl)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (273 mg, 0.53 mmol) in DMF (1 mL) slowly at 40° C. After 15 min, the reaction mixture was cooled to ambient temperature (about 22° C.) and a solution of Pd2(dba)3 (12 mg, 0.01 mmol), (o-tol)3P (16 mg, 0.05 mmol), and 1-fluoro-4-iodobenzene (80 μL, 0.69 mmol) in DMF (900 μL) was added to the reaction and the reaction was warmed back to 40° C. and stirring continued for 1.5 hr. The mixture was cooled, diluted with EtOAc (2 mL), and filtered through a 0.45 micrometer (μm) fritted filter disc. The solution was diluted with EtOAc (100 mL), washed with H2O (3×), dried over MgSO4, filtered, and concentrated. Purification by column chromatography (SiO2, 0→20% EtOAc/hexanes) gave the title compound (96 mg, 38%) as a white, glassy solid: mp 58-66° C.; 1H NMR (300 MHz, CDCl3) δ 7.08 (m, 2H), 6.95 (m, 2H), 5.22-5.14 (m, 3H), 4.93 (m, 1H), 4.80 (m, 1H), 3.46 (m, 1H), 3.00-2.80 (m, 2H), 2.64 (m, 2H), 1.44 (s, 9H), 1.31 (d, J=6.4 Hz, 3H), 1.25 (d, J=7.0 Hz, 3H), 1.25 (d, J=7.0 Hz, 3H); ESIMS m/z 503.3 ([M+Na]+).

Provenance & Evidence