Nitromethane → 2-(3-Fluoro-phenoxy)-5-(2-nitro-ethyl)-pyridine

HRID 1891706Notes

Reaction equation

HRID 1891706 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][C:6]1[N:11]=[CH:10][C:9]([CH:12]=O)=[CH:8][CH:7]=1.[N+:17]([CH3:20])([O-:19])=[O:18].C([O-])(=O)C.[NH4+].[BH4-].[Na+].C(=O)([O-])O.[Na+]>O.C(O)(=O)C.CS(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH2:20][N+:17]([O-:19])=[O:18])=[CH:10][N:11]=1

Participants

9

Reactant 5

HCID 6375NitromethaneHCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 59255292HCID 59255292, compound

Product 1

HCID 592554082-(3-Fluoro-phenoxy)-5-(2-nitro-ethyl)-pyridineYield 66%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To an acetic acid (20 mL) solution of 6-(3-fluoro-phenoxy)-pyridine-3-carbaldehyde (2.47 g, 11.4 mmol) described in Manufacturing Example 71-1-2 was added nitromethane (3.09 mL, 57.0 mmol) and ammonium acetate (1.76 g, 22.8 mmol), which was stirred for 6 hours at 100° C. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. To a dimethyl sulfoxide (35 mL) and acetic acid (5 mL) solution of the residue was added sodium borohydride (681 mg, 17.1 mmol), which was stirred for 40 minutes at room temperature. Sodium hydrogencarbonate and water were added to the reaction mixture at room temperature while cooling appropriately, which was then extracted with ethyl acetate. The organic layer was separated, washed with 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 (heptane:ethyl acetate=2:1) to obtain the title compound (1.96 g, 66%).

Workup

  1. extractionwhich was then extracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under a reduced pressure
  7. stirringwas stirred for 40 minutes at room temperature
  8. temperaturewhile cooling appropriately
  9. extractionwhich was then extracted with ethyl acetate
  10. customThe organic layer was separated
  11. washwashed with 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 (heptane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-b3cd07d4c7634c40813c102ad0666551
Source dataset
uspto-grants-2013_08
Patent number
US08507530B2

Reaction notes

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