Sodium Azide → HCID 86701270, compound

Temperature

60 °C

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]+).

1. customThe resulting reaction mixture
2. customThe reaction was partitioned between sat'd aqueous NaHCO3 solution (20 mL) and EtOAc (25 mL)
3. customthe phases were separated
4. extractionThe aqueous phase was extracted with additional EtOAc (2×25 mL)
5. dry with materialthe combined EtOAc extracts were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. dissolutionThe crude residue was dissolved in DMF/H2O (1 mL/1 mL)
9. stirringthe reaction mixture was stirred at room temperature overnight
10. customThe reaction was partitioned between sat'd aqueous NaHCO3 solution (15 mL) and EtOAc (20 mL)
11. customthe phases were separated
12. extractionThe aqueous phase was extracted with additional EtOAc (2×20 mL)
13. dry with materialthe combined EtOAc extracts were dried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated to dryness
16. customThe crude residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient)

ORD record

ord-56b18bf5fad54f2096d15655414640cd

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09131690B2