Aniline → (2-Chloro-3-fluoro-6-nitrophenyl)phenylamine

HRID 242930Notes

Reaction equation

[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Cl:18][C:19]1[C:24](F)=[C:23]([N+:26]([O-:28])=[O:27])[CH:22]=[CH:21][C:20]=1[F:29]>C1COCC1>[Cl:18][C:19]1[C:20]([F:29])=[CH:21][CH:22]=[C:23]([N+:26]([O-:28])=[O:27])[C:24]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

Conditions

Temperature: -78 °C

Procedure

LiHMDS (1.0M in THF, 10.3 mL, 10.3 mmol) was added dropwise to a stirred solution of aniline (505 mg, 5.43 mmol) in anhydrous THF (10 mL) under a nitrogen atmosphere at −78° C. After 10 min stirring at −78° C., a solution of 2-chloro-1,3-difluoro-4-nitrobenzene (1.0 g, 5.17 mmol) in THF (5 mL) was added and stirring at −78° C. was continued for 30 min. The reaction mixture was quenched by addition of water then extracted with EtOAc (×3). The combined organic fractions were washed with brine, dried (MgSO4), concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-70% EtOAc in cyclohexane) to afford the title compound (1.28 g, 93%). 1H NMR (CDCl3, 400 MHz): δ 8.70 (1H, s), 8.15 (1H, dd, J=9.44, 5.61 Hz), 7.36-7.28 (2H, m), 7.12 (1H, t, J=7.44 Hz), 6.98-6.86 (3H, m).

Workup

stirringstirring at −78° C.
waitwas continued for 30 min
customThe reaction mixture was quenched by addition of water
extractionthen extracted with EtOAc (×3)
washThe combined organic fractions were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-70% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-7256a6fe0d474bbd92a9b51f1620b1aa
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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