Aniline → (3-Fluoro-2-methyl-6-nitrophenyl)phenylamine

HRID 242981Notes

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.[F:18][C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[C:21](F)[C:20]=1[CH3:29]>C1COCC1>[F:18][C:19]1[C:20]([CH3:29])=[C:21]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=1

Participants

Conditions

Temperature: -78 °C

Procedure

LiHMDS (1.0M in THF, 12.9 mL, 12.9 mmol) was added dropwise to a stirred solution of aniline (633 mg, 6.79 mmol) in anhydrous THF (10 mL) under a nitrogen atmosphere at −78° C. After 10 min stirring at −78° C., a solution of 1,3-difluoro-2-methyl-4-nitrobenzene (1.12 g, 6.47 mmol) in THF (5 mL) was added and stirring was continued for 30 min. The reaction mixture was quenched by addition of water and was diluted with EtOAc. The resulting emulsion was filtered through Celite® and the organic fraction separated, washed with brine and dried (MgSO4). The volatiles were removed in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane) to afford the title compound (1.5 g, 94%). 1H NMR (CDCl3, 400 MHz): δ 8.74 (1H, br s), 8.07 (1H, dd, J=9.34, 5.86 Hz), 7.30-7.23 (2H, m), 7.03 (1H, t, J=7.41 Hz), 6.85-6.78 (3H, m), 1.92 (3H, d, J=2.87 Hz).

Workup

stirringstirring
waitwas continued for 30 min
customThe reaction mixture was quenched by addition of water
additionwas diluted with EtOAc
filtrationThe resulting emulsion was filtered through Celite®
customthe organic fraction separated
washwashed with brine
dry with materialdried (MgSO4)
customThe volatiles were removed in vacuo
customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-bdff17d0ecf1409fb714c2f3273c32c8
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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