Nitromethane → 1-Fluoro-2-[4-(2-nitroethyl)phenoxy]benzene

HRID 1693995Notes

Reaction equation

HRID 1693995 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1.[N+:17]([CH3:20])([O-:19])=[O:18].C([O-])(=O)C.[NH4+].[BH4-].[Na+]>O.C(O)(=O)C.CS(C)=O.C(OCC)(=O)C>[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][CH2:20][N+:17]([O-:19])=[O:18])=[CH:7][CH:6]=1

Participants

9

Reactant 4

HCID 6375NitromethaneHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 107987454-(2-Fluorophenoxy)benzaldehyde

Product 1

HCID 592550991-Fluoro-2-[4-(2-nitroethyl)phenoxy]benzeneYield 49.6%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolvent2×HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To an acetic acid (30.0 mL) solution of 4-(2-fluoro-phenoxy)-benzaldehyde (3.00 g, 13.9 mmol) described in Manufacturing Example 83-1-1 were added nitromethane (4.24 g, 69.5 mmol) and ammonium acetate (2.14 g, 27.8 mmol) under nitrogen atmosphere, which was stirred for 3 hours at 110° C. Water and ethyl acetate were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure to obtain a crude product (3.60 g). To a dimethyl sulfoxide (50.0 mL) solution of this crude product (3.60 g) and acetic acid (3.00 mL) was added sodium borohydride (789 mg, 20.9 mmol) at room temperature while cooling appropriately, which was stirred for 20 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:10→1:5) to obtain the title compound (1.80 g, 49.6%).

Workup

  1. extractionthe organic layer was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under a reduced pressure
  6. customto obtain a crude product (3.60 g)
  7. temperaturewhile cooling appropriately
  8. stirringwhich was stirred for 20 minutes at room temperature
  9. temperaturewhile cooling appropriately
  10. extractionThe reaction mixture was extracted with ethyl acetate
  11. washthe organic layer was washed with water and saturated aqueous sodium chloride
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationThe filtrate was concentrated under a reduced pressure
  15. customthe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:10→1:5)

Sources & evidence

ORD record
ord-9420d3648d6f4d2e88eab090c2a37d3d
Source dataset
uspto-grants-2012_04
Patent number
US08158657B2

Reaction notes

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