Ammonium Chloride → (3S,4R,7S)-4-azido-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-3-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(5,8-dioxabicyclo[5.1.0]octan-4-yl)-1-methyl-4-nitro-pyrazole (2.7 g, 11.3 mmol, intermediate 19) in MeOH/water (60 mL/15 mL) was added ammonium chloride (1.51 g, 28.3 mmol) and sodium azide (3.67 g, 56.5 mmol). The mixture was heated at 70° C. behind a blast shield for 4 hr. The MeOH was removed under reduced pressure and the aqueous residue extracted with EtOAc (100 mL). The organic layer was washed with aqueous NaHCO3 (3×20 mL), passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) followed by chiral SFC chromatography gave (3S,4R,7S)-4-azido-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-3-ol as the second eluting isomer as a clear gum (1.4 g, 41%). 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 5.43-5.37 (m, 1H), 4.18 (dd, J=13.9, 2.1 Hz, 1H), 4.06 (s, 3H), 3.97-3.77 (m, 3H), 2.45 (d, J=3.9 Hz, 1H), 2.32-2.09 (m, 2H), 2.10-1.85 (m, 2H).

Provenance & Evidence