Aniline → 6-Fluoro-3-nitro-2-phenylaminobenzonitrile

HRID 242966Notes

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[C:19]1[C:26]([N+:27]([O-:29])=[O:28])=[CH:25][CH:24]=[C:23]([F:30])[C:20]=1[C:21]#[N:22]>C1COCC1>[F:30][C:23]1[C:20]([C:21]#[N:22])=[C:19]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:26]([N+:27]([O-:29])=[O:28])=[CH:25][CH:24]=1

Participants

Conditions

Temperature: -78 °C

Procedure

LiHMDS (1.0M in THF, 38 mL, 38.0 mmol) was added dropwise to a stirred solution of aniline (1.86 g, 19.9 mmol) in anhydrous THF (30 mL) under a nitrogen atmosphere at −78° C. After 10 min stirring at −78° C., a solution of 2,6-difluoro-3-nitrobenzonitrile (3.5 g, 19.0 mmol) in THF (15 mL) was added and stirring at −78° C. continued for 30 min. The crude mixture was quenched with water and diluted with EtOAc. The resulting emulsion was filtered through a pad of Celite® and the organic fraction separated, 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 (2.7 g, 55%). 1H NMR (CDCl3, 400 MHz): δ 9.94 (1H, br s), 8.51 (1H, dd, J=9.50, 5.88 Hz), 7.51-7.21 (5H, m), 6.68 (1H, dd, J=9.50, 7.46 Hz).

Workup

stirringstirring at −78° C.
waitcontinued for 30 min
customThe crude mixture was quenched with water
additiondiluted with EtOAc
filtrationThe resulting emulsion was filtered through a pad of Celite®
customthe organic fraction separated
washwashed 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-6dc42c5755244d43870a60c61a702aa9
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

Loading…