Hydrogen Peroxide → 1,3-Difluoro-2-methoxy-4-nitrobenzene

HRID 243236Notes

Reaction equation

HRID 243236 reaction equation
FC(F)(F)C(OC(=O)C(F)(F)F)=[O:4].OO.[F:16][C:17]1[C:22]([O:23][CH3:24])=[C:21]([F:25])[CH:20]=[CH:19][C:18]=1[NH2:26].[Cl-].[Na+].[OH2:29]>C(Cl)Cl>[F:25][C:21]1[CH:20]=[CH:19][C:18]([N+:26]([O-:4])=[O:29])=[C:17]([F:16])[C:22]=1[O:23][CH3:24]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 9845Trifluoroacetic anhydrideHCID 38651622,4-Difluoro-3-methoxyanilineHCID 57417360Sodium chloride; water

Product 1

HCID 681577701,3-Difluoro-2-methoxy-4-nitrobenzeneYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of trifluoroacetic anhydride (26.2 mL, 0.19 mol) in DCM (100 mL) at 0° C. was added, dropwise, hydrogen peroxide (50% in water, 12.9 mL, 0.17 mol) and the reaction mixture was stirred at 0° C. for 1.5 h. 2,4-Difluoro-3-methoxyphenylamine (3 g, 18.9 mmol) was added as a solution in DCM (20 mL) and the reaction mixture stirred at RT for 3 h. The reaction mixture was diluted with brine and extracted with DCM (3×30 mL). The combined organic fractions were washed with sat. aq. NaHCO3 solution, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% Et2O in cyclohexane) to give the title compound as a colourless solid (2.03 g, 57%). 1H NMR 400 MHz δ (CDCl3): 7.83-7.76 (1H, m), 7.03 (1H, td, J=9.4, 2.5 Hz), 4.08 (3H, t, J=1.1 Hz).

Workup

  1. extractionextracted with DCM (3×30 mL)
  2. washThe combined organic fractions were washed with sat. aq. NaHCO3 solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% Et2O in cyclohexane)

Sources & evidence

ORD record
ord-c99f3b63bec646a9971dad90cb26ee8c
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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