Ammonium Chloride → 2-azido-5-fluoro-5-(1-methyl-4-nitro-1H-pyrazol-5-yl)cycloheptanol

HRID 521870Notes

Reaction equation

[F:1][C:2]1([C:10]2[N:14]([CH3:15])[N:13]=[CH:12][C:11]=2[N+:16]([O-:18])=[O:17])[CH2:9][CH2:8][CH:7]2[CH:5]([O:6]2)[CH2:4][CH2:3]1.[Cl-].[NH4+].[N-:21]=[N+:22]=[N-:23].[Na+]>CN(C=O)C.O>[N:21]([CH:7]1[CH2:8][CH2:9][C:2]([F:1])([C:10]2[N:14]([CH3:15])[N:13]=[CH:12][C:11]=2[N+:16]([O-:18])=[O:17])[CH2:3][CH2:4][CH:5]1[OH:6])=[N+:22]=[N-:23]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 5-(4-fluoro-8-oxabicyclo[5.1.0]octan-4-yl)-1-methyl-4-nitro-1H-pyrazole (2.75 g, 10.8 mmol, Intermediate 155) in DMF/water (35 mL/10 mL) was treated with ammonium chloride (1.43 g, 27.0 mmol) and sodium azide (3.5 g, 53.9 mmol) and the mixture was heated at 100° C. behind a blast shield for 18 hr. The reaction mixture was extracted with EtOAc (200 mL) and the organic layer was washed with water (8×30 mL), washed with brine (30 mL), separated, dried over MgSO4, and concentrated under reduced pressure. Purification via silica gel column chromatography (30-40% EtOAc/isohexane) gave 2-azido-5-fluoro-5-(1-methyl-4-nitro-1H-pyrazol-5-yl)cycloheptanol as the second eluting isomer as a white solid (2.16 g, 67%). 1H NMR (400 MHz, CDCl3) δ 8.06 and 8.05 (2s, 1H), 4.08 and 4.06 (2s, 3H), 3.88-3.78 (m, 1H), 3.65-3.58 (m, 1H), 2.87-2.55 (m, 2H), 2.31-2.21 (m, 2H), 2.18-2.00 (m, 3H), 1.98-1.85 (m, 2H).

Workup

extractionThe reaction mixture was extracted with EtOAc (200 mL)
washthe organic layer was washed with water (8×30 mL)
washwashed with brine (30 mL)
customseparated
dry with materialdried over MgSO4
concentrationconcentrated under reduced pressure
customPurification via silica gel column chromatography (30-40% EtOAc/isohexane)

Sources & evidence

ORD record: ord-54889da37f2947139062ec15bd9a549e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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