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

HRID 1915816Notes

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 (260 mg, 1.02 mmol) in DMF/water (10 mL/1 mL) was treated with ammonium chloride (135 mg, 2.55 mmol) and sodium azide (332 mg, 5.1 mmol) and the mixture was heated at 100° C. for 48 hrs. The reaction mixture was extracted with EtOAc (100 mL) and the organic layer was washed with water (7×20 mL), washed with brine (20 mL), separated, dried over MgSO4, and concentrated under reduced pressure. Purification via silica gel column chromatography (40% EtOAc/isohexane) gave 2-azido-5-fluoro-5-(1-methyl-4-nitro-1H-pyrazol-5-yl)cycloheptanol as a white solid (145 mg, 48%). 1H NMR (400 MHz, CDCl3) δ 8.06 and 8.05 (2s, 1H), 4.08 and 4.06 (2s, 3H), 3.83 (dd, J=10.7, 8.2 Hz, 1H), 3.65-3.58 (m, 1H), 2.87-2.55 (m, 2H), 2.33-2.21 (m, 2H), 2.17-1.98 (m, 3H), 1.98-1.84 (m, 2H).

Workup

extractionThe reaction mixture was extracted with EtOAc (100 mL)
washthe organic layer was washed with water (7×20 mL)
washwashed with brine (20 mL)
customseparated
dry with materialdried over MgSO4
concentrationconcentrated under reduced pressure
customPurification via silica gel column chromatography (40% EtOAc/isohexane)

Sources & evidence

ORD record: ord-acfd5ce4cd1845f0a1fd319c3fc78d11
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08614206B2

Reaction notes

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