Ammonium Chloride → (5-Fluoro-2-nitrophenyl)-(5-fluoropyridin-3-yl)amine

HRID 243102

Reaction equation

[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH2:11][C:12]1[CH:13]=[N:14][CH:15]=[C:16]([F:18])[CH:17]=1.F[C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[N+:27]([O-:29])=[O:28].[NH4+].[Cl-]>C1COCC1>[F:26][C:24]1[CH:23]=[CH:22][C:21]([N+:27]([O-:29])=[O:28])=[C:20]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([F:18])[CH:17]=2)[CH:25]=1

Participants

Conditions

Temperature: -78 °C

Procedure

LiHMDS (1.0M in THF, 10.0 mL, 10.0 mmol) was added dropwise to a stirred solution of 3-amino-5-fluoropyridine (588 mg, 5.26 mmol) in anhydrous THF (10 mL) under a nitrogen atmosphere at −78° C. After 20 min 2,4-difluoro-1-nitrobenzene (0.55 mL, 5.0 mmol) was added and stirring at −78° C. was 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 0-100% EtOAc in DCM) to afford the title compound as an orange solid (428 mg, 34%). LCMS (Method C): RT 3.27 min [M+H]+ 252.16

Workup

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 0-100% EtOAc in DCM)

Sources & evidence

ORD record: ord-eedb0e9ffe5c4ad9a0ab08ec1655f8d0
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Linked notes

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