2-Methyl-4-nitrophenol → 1-(Difluoromethoxy)-2-methyl-4-nitrobenzene

HRID 2110136Notes

Reaction equation

HRID 2110136 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:19]([F:24])([F:23])C([O-])=O.[Na+]>CN(C)C=O.O>[F:23][CH:19]([F:24])[O:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[CH3:1]

Participants

6

Reactant 3

HCID 74422-Methyl-4-nitrophenolHCID 10796Cesium carbonateHCID 2734985Sodium chlorodifluoroacetate

Product 1

HCID 133147061-(Difluoromethoxy)-2-methyl-4-nitrobenzeneYield 86.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-methyl-4-nitrophenol (14 g, 91.50 mmol) in dimethylformamide (120 mL) and water (25 mL) was added Cs2CO3 (41.8 g, 128.22 mmol), and sodium 2-chloro-2,2-difluoroacetate (32 g, 209.84 mmol). The resulting solution was stirred for 20 minutes at room temperature, then for an additional 3 hours at 100° C. The reaction solution was cooled to room temperature before the addition of 100 ml of H2O. The resulting solution was extracted with EtOAc (4×100 ml) and the combined organic layers were washed with H2O (2×150 mL), dried over Na2SO4, concentrated in vacuo. The residue was purified by silica gel column chromatography to provide 16 g (86%) of 1-(difluoromethoxy)-2-methyl-4-nitrobenzene.

Workup

  1. waitfor an additional 3 hours at 100° C
  2. extractionThe resulting solution was extracted with EtOAc (4×100 ml)
  3. washthe combined organic layers were washed with H2O (2×150 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ab4986c9cc964a6591c75f506284d803
Source dataset
uspto-grants-2009_04
Patent number
US07517884B2

Reaction notes

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