Nitromethane → 3-(2-Nitroethyl)-5-phenoxypyridine

HRID 1694096Notes

Reaction equation

HRID 1694096 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([CH:14]=O)[CH:11]=[N:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:16]([CH3:19])([O-:18])=[O:17].C([O-])(=O)C.[NH4+].[BH4-].[Na+].C(=O)([O-])O.[Na+]>CS(C)=O.O.C(O)(=O)C>[N+:16]([CH2:19][CH2:14][C:10]1[CH:11]=[N:12][CH:13]=[C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:9]=1)([O-:18])=[O:17]

Participants

9

Reactant 5

HCID 6375NitromethaneHCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 59255438HCID 59255438, compound

Product 1

HCID 592554813-(2-Nitroethyl)-5-phenoxypyridineYield 28.2%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To an acetic acid (15 mL) solution of 5-phenoxy-pyridine-3-carbaldehyde (607 mg, 3.05 mmol) described in Manufacturing Example 145-1-3 were added nitromethane (826 μL, 15.3 mmol) and ammonium acetate (470 mg, 6.10 mmol), which was stirred for 3 hours at 100° C. under nitrogen atmosphere. Water was added at room temperature 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 (10 mL) and acetic acid (1 mL) was added sodium borohydride (182 mg, 4.58 mmol), which was stirred for 20 minutes at room temperature. Sodium hydrogencarbonate and water were added to the reaction mixture at room temperature while cooling appropriately, 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 (210 mg, 28%).

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 20 minutes at room temperature
  8. temperaturewhile cooling appropriately
  9. extractionwhich was 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=1:1)

Sources & evidence

ORD record
ord-efc0230b49354db5842c6655b6d92837
Source dataset
uspto-grants-2012_04
Patent number
US08158657B2

Reaction notes

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