Cesium carbonate → 4-Bromo-3-(2,4-difluorophenoxy)-2-nitroaniline

HRID 1056934Notes

Reaction equation

[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1F.C(=O)([O-])[O-].[Cs+].[Cs+].[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[OH:27]>CS(C)=O.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[O:27][C:21]1[CH:22]=[CH:23][C:24]([F:26])=[CH:25][C:20]=1[F:19]

Participants

Conditions

Temperature: 20 °C

Procedure

A solution of 4-bromo-3-fluoro-2-nitroaniline (0.100 g, 0.426 mmol) [Combi-Blocks, AN-2785] and cesium carbonate (0.167 g, 0.511 mmol) in dimethyl sulfoxide (0.47 mL) was treated with 2,4-difluorophenol (0.083 mL, 0.512 mmol) and stirred at 20° C. for 30 min and heated at 110° C. for 30 min. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated and washed with water and brine, dried with magnesium sulfate, filtered, and concentrated to give a crude residue. Purification by flash column chromatography (100% hexanes to 40% EtOAc/hexanes) gave the desired product (140 mg, 95%) as an orange/brown oil. LCMS calculated for C12H8BrF2N2O3 (M+H)+: m/z=345.0, 347.0. found: 344.9, 346.9.

Workup

temperatureheated at 110° C. for 30 min
customThe organic layer was separated
washwashed with water and brine
dry with materialdried with magnesium sulfate
filtrationfiltered
concentrationconcentrated
customto give a crude residue
customPurification by flash column chromatography (100% hexanes to 40% EtOAc/hexanes)

Sources & evidence

ORD record: ord-8349fd5aedb74ad78f3617370996964e
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09399640B2

Reaction notes

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