Nitromethane → 5-(2-Nitroethyl)-2-(pyridin-3-yloxy)pyridine

HRID 78090Notes

Reaction equation

HRID 78090 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[N:13]=[CH:12][C:11]([CH:14]=O)=[CH:10][CH:9]=2)[CH:2]=1.[N+:16]([CH3:19])([O-:18])=[O:17].C([O-])(=O)C.[NH4+].[BH4-].[Na+]>O.C(O)(=O)C>[N+:16]([CH2:19][CH2:14][C:11]1[CH:10]=[CH:9][C:8]([O:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[N:13][CH:12]=1)([O-:18])=[O:17]

Participants

7

Reactant 4

HCID 6375NitromethaneHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 592551936-(Pyridin-3-yloxy)-pyridine-3-carbaldehyde

Product 1

HCID 592551135-(2-Nitroethyl)-2-(pyridin-3-yloxy)pyridineYield 26%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 6-(pyridin-3-yloxy)-pyridine-3-carbaldehyde (505.1 mg, 2.52 mmol) described in Manufacturing Example 100-1-1, nitromethane (680 μL, 12.6 mmol), ammonium acetate (388 mg, 5.04 mmol), and acetic acid (20 mL) was stirred for 2.5 hours at 140° C. This reaction mixture was cooled to room temperature and partitioned into water and ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. To a mixture of this residue in dimethyl sulfoxide (20 mL) and acetic acid (2 mL) was added sodium borohydride (114.0 mg, 3.02 mmol) at room temperature, which was stirred for 15 minutes. Water was added to this reaction mixture, which was extracted with ethyl acetate. The organic layer was separated, 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 silica gel column chromatography (heptane: ethyl acetate=2:1) to obtain the title compound (157.3 mg, 26%).

Workup

  1. temperatureThis reaction mixture was cooled to room temperature
  2. custompartitioned into water and ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under a reduced pressure
  8. additionTo a mixture of this residue in dimethyl sulfoxide (20 mL)
  9. stirringwhich was stirred for 15 minutes
  10. extractionwas extracted with ethyl acetate
  11. customThe organic layer was separated
  12. washwashed with water and saturated aqueous sodium chloride
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated under a reduced pressure
  16. customthe residue was purified by silica gel column chromatography (heptane: ethyl acetate=2:1)

Sources & evidence

ORD record
ord-ac0facf305674f53896e8cdd72f75691
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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