Aniline → 5-Fluoro-2-nitro-N-phenylaniline

HRID 242787Notes

Reaction equation

HRID 242787 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:11]1([NH2:17])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.F[C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27].[NH4+].[Cl-]>C1COCC1>[F:25][C:23]1[CH:22]=[CH:21][C:20]([N+:26]([O-:28])=[O:27])=[C:19]([NH:17][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:24]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 25517Ammonium ChlorideHCID 679672,4-DifluoronitrobenzeneHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 189929835-Fluoro-2-nitro-N-phenylanilineYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LiHMDS (1.0M in THF, 12.57 mL) was added dropwise to a stirred solution of phenylamine (600 μL, 6.60 mmol) in ahydrous THF (10 mL) under a nitrogen atmosphere at −78° C. After 30 min, a solution of 2,4-difluoro-1-nitrobenzene (690 μL, 6.29 mmol) in THF (10 mL) was added and stirring was continued for 1 h. The solution was poured into an aqueous solution of NH4Cl (100 mL) and extracted with EtOAc (×3). The combined organic layers were dried and concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) affording (5-Fluoro-2-nitrophenyl)phenylamine as a yellow/orange solid (1.37 g, 94%). 1H NMR (CDCl3, 400 MHz): δ 9.66 (1H, s), 8.28 (1H, dd, J=9.48, 6.01 Hz), 7.47 (2H, t, J=7.63 Hz), 7.36-7.24 (3H, m), 6.82 (1H, dd, J=11.38, 2.61 Hz), 6.53-6.44 (1H, m).

Workup

  1. waitwas continued for 1 h
  2. extractionextracted with EtOAc (×3)
  3. customThe combined organic layers were dried
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-67849706081d4f108cad9a8995652f2a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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