Nitromethane → 5-(2-Nitro-ethyl)-2-(pyridin-2-yloxymethyl)-pyridine

HRID 1891871Notes

Reaction equation

HRID 1891871 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][CH2:8][C:9]1[N:14]=[CH:13][C:12]([CH:15]=O)=[CH:11][CH:10]=1.[N+:17]([CH3:20])([O-:19])=[O:18].C([O-])(=O)C.[NH4+].[BH4-].[Na+].C(=O)([O-])O.[Na+]>CS(C)=O.O.C(O)(=O)C>[N+:17]([CH2:20][CH2:15][C:12]1[CH:11]=[CH:10][C:9]([CH2:8][O:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[N:14][CH:13]=1)([O-:19])=[O:18]

Participants

9

Reactant 5

HCID 6375NitromethaneHCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 592553126-(Pyridin-2-yloxymethyl)-pyridine-3-carbaldehyde

Product 1

HCID 592554515-(2-Nitro-ethyl)-2-(pyridin-2-yloxymethyl)-pyridineYield 15.3%

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-(pyridine-2-yloxymethyl)-pyridine-3-carbaldehyde (504 mg, 2.35 mmol) described in Manufacturing Example 154-1-6 were added nitromethane (635 μL, 11.8 mmol) and ammonium acetate (363 mg, 4.71 mmol), which was stirred for 4 hours at 100° C. under nitrogen atmosphere. Water was added to the reaction mixture at room temperature, which was 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 solution of this residue in dimethyl sulfoxide (25 mL) and acetic acid (2.5 mL) was added sodium borohydride (178 mg, 4.71 mmol), which was stirred for 25 minutes at room temperature. Sodium hydrogencarbonate and water were added to the reaction mixture at room temperature, which was 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=1:1) to obtain the title compound (93 mg, 15%).

Workup

  1. extractionwhich was 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 25 minutes at room temperature
  8. extractionwhich was extracted with ethyl acetate
  9. customThe organic layer was separated
  10. washwashed with saturated aqueous sodium chloride
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated under a reduced pressure
  14. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-ed7a3caf0a1943f9974e6ae2c131e148
Source dataset
uspto-grants-2013_08
Patent number
US08507530B2

Reaction notes

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