4-Aminopyridine → (5-Fluoro-2-nitrophenyl)-pyridin-4-yl-amine

HRID 243098Notes

Reaction equation

CC(C)([O-])C.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1.F[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[N+:22]([O-:24])=[O:23].[NH4+].[Cl-]>C1COCC1>[F:21][C:19]1[CH:18]=[CH:17][C:16]([N+:22]([O-:24])=[O:23])=[C:15]([NH:7][C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[CH:20]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Potassium tert-butoxide (898 mg, 8.0 mmol) was added to a stirred solution of 4-aminopyridine (376 mg, 4.00 mmol) in anhydrous THF (5 mL) under a nitrogen atmosphere at 0° C. After 15 min stirring at 0° C., 2,4-difluoro-1-nitrobenzene (0.44 mL, 4.0 mmol) in anhydrous THF (5 mL) was added and stirring at 0° C. continued for 1 h. The reaction mixture was poured into a saturated aqueous solution of NH4Cl (50 mL). The aqueous phase was extracted with EtOAc (×2) and the combined organic fractions washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) to afford the title compound as a yellow solid (557 mg, 60%). LCMS (Method C): RT 1.26 min [M+H]+ 234.12

Workup

stirringstirring at 0° C.
waitcontinued for 1 h
extractionThe aqueous phase was extracted with EtOAc (×2)
washthe combined organic fractions washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)

Sources & evidence

ORD record: ord-be6245a44a7041f58f79d5b06e05f141
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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