Sodium Azide → HCID 86701270, compound

Participants

Reaction Conditions

Reaction Steps

To a solution (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-6-methyl-8-(2(methylsulfonyloxy)ethyl)-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (140 mg, 0.28 mmol) in DMF (3 mL) at room temperature (about 22° C.) was added NaN3 (37 mg, 0.57 mmol). The resulting reaction mixture was heated to 60° C. and stirred for 3 h. The reaction was partitioned between sat'd aqueous NaHCO3 solution (20 mL) and EtOAc (25 mL) and the phases were separated. The aqueous phase was extracted with additional EtOAc (2×25 mL), and the combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated to dryness. The crude residue was dissolved in DMF/H2O (1 mL/1 mL) and the resulting solution was treated with 1-chloro-3-ethynylbenzene (39 mg, 0.28 mol), CuSO4 (4 mg, 0.025 mmol), and sodium ascorbate (22 mg, 0.11 mmol), and the reaction mixture was stirred at room temperature overnight. The reaction was partitioned between sat'd aqueous NaHCO3 solution (15 mL) and EtOAc (20 mL) and the phases were separated. The aqueous phase was extracted with additional EtOAc (2×20 mL), and the combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated to dryness. The crude residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient) to afford the title compound (105 mg, 64%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.82 (d, J=1.7 Hz, 1H), 7.70 (dq, J=3.2, 1.5 Hz, 2H), 7.33 (ddd, J=10.9, 8.0, 4.9 Hz, 2H), 5.40-5.15 (m, 2H), 5.08 (t, J=9.8 Hz, 1H), 4.82 (dd, J=14.6, 4.8 Hz, 2H), 4.51-4.24 (m, 2H), 3.63 (s, 1H), 2.66-2.49 (m, 2H), 2.42-2.25 (m, 1H), 2.14-2.00 (m, 1H), 1.45 (s, 9H), 1.27 (dd, J=6.7, 1.3 Hz, 3H), 1.18 (d, J=7.1 Hz, 6H); ESIMS m/z 579 ([M+H]+).

Provenance & Evidence