Methanol → 5-Azido-2-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-ol

HRID 521846Notes

Reaction equation

[CH:1]12[O:8][CH:7]1[CH2:6][CH:5]([C:9]1[N:13]([CH3:14])[N:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])[O:4][CH2:3][CH2:2]2.CO.[Cl-].[NH4+].[N-:22]=[N+:23]=[N-:24].[Na+]>O>[N:22]([CH:1]1[CH2:2][CH2:3][O:4][CH:5]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[CH2:6][CH:7]1[OH:8])=[N+:23]=[N-:24]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 5-(4,8-dioxabicyclo[5.1.0]octan-5-yl)-1-methyl-4-nitro-pyrazole (1.04 g, 4.35 mmol) in 4:1 MeOH:water (30 mL) was added ammonium chloride (0.58 g, 10.88 mmol) and sodium azide (1.41 g, 21.75 mmol). The mixture was heated at 70° C. behind a blast screen for 16 hr. The MeOH was removed under reduced pressure and EtOAc (20 mL) added. The organic layer was washed with saturated aqueous NaHCO3 (20 mL), passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel chromatography (0-60% EtOAc/isohexane) gave 5-azido-2-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-ol as a pale yellow gum (718 mg, 58% yield). 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 5.76 (dd, J=9.3, 3.2 Hz, 1H), 4.18-4.10 (m, 1H), 4.08-4.04 (m, 4H), 3.91 (ddd, J=9.4, 6.6, 6.2 Hz, 1H), 3.79 (ddd, J=12.6, 8.6, 3.5 Hz, 1H), 2.44 (ddd, J=15.3, 9.4, 3.8 Hz, 1H), 2.37-2.29 (m, 1H), 2.24 (d, J=3.2 Hz, 1H), 2.12 (ddd, J=15.3, 5.7, 3.2 Hz, 1H), 2.06-1.96 (m, 1H).

Workup

customThe MeOH was removed under reduced pressure and EtOAc (20 mL)
additionadded
washThe organic layer was washed with saturated aqueous NaHCO3 (20 mL)
custompassed through a phase separation cartridge
concentrationconcentrated under reduced pressure
customPurification via silica gel chromatography (0-60% EtOAc/isohexane)

Sources & evidence

ORD record: ord-01b094f2e6324da8b6d79f48250dc81c
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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