Ammonium Chloride → 3-Amino-6-fluoro-2-phenylaminobenzonitrile

HRID 242967Notes

Reaction equation

[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:5]([N+:17]([O-])=O)=[CH:4][CH:3]=1.[NH4+].[Cl-]>CO.O.[Fe]>[NH2:17][C:5]1[C:6]([NH:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[C:7]([C:2]([F:1])=[CH:3][CH:4]=1)[C:8]#[N:9]

Participants

Conditions

Temperature: 90 °C

Procedure

To a mixture of 6-fluoro-3-nitro-2-phenylaminobenzonitrile (2.7 g, 10.5 mmol) in a mixture of MeOH (50 mL) and water (20 mL) were added NH4Cl (3.23 g, 62.9 mmol) and iron powder (2.3 g, 41.9 mmol) and the reaction mixture was heated at 90° C. for 1 h. After cooling to RT, the solid was filtered through a pad of Celite® and the filtrate concentrated in vacuo. The resulting residue was partitioned between EtOAc and water and the aqueous phase was extracted with EtOAc (×3). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane) to afford the title compound (930 mg, 39%). LCMS (Method B): RT 3.27 min [M+H]+ 227.8.

Workup

temperatureAfter cooling to RT
filtrationthe solid was filtered through a pad of Celite®
concentrationthe filtrate concentrated in vacuo
customThe resulting residue was partitioned between EtOAc and water
extractionthe aqueous phase was extracted with EtOAc (×3)
washThe combined organic fractions were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-da7c8e982a454149b043004feefdfcf1
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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