Acetic Acid → 2-((2-Methoxy-4-(trifluoromethyl)phenyl)amino)-5-nitrophenol

HRID 528637Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[OH:11].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=1[O:29][CH3:30].C(O)(=O)C.C(Cl)Cl.CO.[NH4+].[OH-]>CN(C=O)C.[Cu]I.CCOC(C)=O>[CH3:30][O:29][C:20]1[CH:21]=[C:22]([C:25]([F:26])([F:27])[F:28])[CH:23]=[CH:24][C:19]=1[NH:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[OH:11]

Participants

Conditions

Temperature: 25 °C

Procedure

Dissolved 2-amino-5-nitrophenol (4.0 g, 26.0 mmol), cesium carbonate (23.25 g, 71.4 mmol), and copper(i) iodide (4.94 g, 26.0 mmol) in DMF (43.3 ml) in a 250 mL sealed tube and stirred at 25° C. for 30 min. Then added 1-bromo-2-methoxy-4-(trifluoromethyl)benzene (5.52 g, 21.63 mmol) and stirred for 18 h at 100° C. Added acetic acid (8.67 ml, 151 mmol) to neutralize base and product. Diluted the reaction with a solution of DCM/MeOH/NH4OH (90:10:1) and filtered through a frit of silica to remove some of the copper and base, rinsing with more of the solution. The collected eluent was concentrated, then purified using silica gel chromatography using a gradient of (0-100%) Hex:EtOAc to yield 2-((2-methoxy-4-(trifluoromethyl)phenyl)amino)-5-nitrophenol (1.75 g, 5.33 mmol, 24.65% yield) as a yellow solid.

Workup

customsealed tube
additionDiluted
filtrationfiltered through a frit of silica
customto remove some of the copper and base
washrinsing with more of the solution
concentrationThe collected eluent was concentrated
custompurified

Sources & evidence

ORD record: ord-78c192b07ca347a39500307d3f60f6bc
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346798B2

Reaction notes

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