Triethylamine → 7-[4-Nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane

HRID 335390

Reaction equation

Cl.[CH:2]12[NH:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.F[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([C:19]([F:22])([F:21])[F:20])[CH:11]=1.C(N(CC)CC)C>C(#N)C>[N+:16]([C:13]1[CH:14]=[CH:15][C:10]([N:8]2[CH:5]3[CH2:6][CH2:7][CH:2]2[CH2:3][CH2:4]3)=[CH:11][C:12]=1[C:19]([F:20])([F:21])[F:22])([O-:18])=[O:17]

Participants

Conditions

Temperature: 80 °C

Procedure

To a flask containing 7-azabicyclo[2.2.1]heptane hydrochloride (8-HCl) (4.6 g, 34.43 mmol, obtained from under a nitrogen atmosphere was added a solution of 4-fluoro-1-nitro-2-(trifluoromethyl)benzene (7) (6.0 g, 28.69 mmol) and triethylamine (8.7 g, 12.00 ml, 86.07 mmol) in acetonitrile (50 ml). The reaction flask was heated at 80° C. under a nitrogen atmosphere for 16 h. The reaction mixture was allowed to cool and then was partitioned between water and dichloromethane. The organic layer was washed with 1 M HCl, dried over Na2SO4, filtered, and concentrated to dryness. Purification by silica gel chromatography (0-10% ethyl acetate in hexanes) yielded 7-[4-nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane (9) as a yellow solid. 1H NMR (400.0 MHz, DMSO-d6) δ 8.03 (d, J=9.1 Hz, 1H), 7.31 (d, J=2.4 Hz, 1H), 7.25 (dd, J=2.6, 9.1 Hz, 1H), 4.59 (s, 2H), 1.69-1.67 (m, 4H), 1.50 (d, J=7.0 Hz, 4H).

Workup

customobtained from under a nitrogen atmosphere
temperatureto cool
customwas partitioned between water and dichloromethane
washThe organic layer was washed with 1 M HCl
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated to dryness
customPurification by silica gel chromatography (0-10% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-d05cad498fc040768faa8a983d15afd2
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08884018B2

Linked notes

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