Nitromethane → 2-(3-(2-Nitro-ethyl)-phenyl)-pyridine

HRID 78044Notes

Reaction equation

HRID 78044 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=1)[CH:10]=O.[N+:15]([CH3:18])([O-:17])=[O:16].C([O-])(=O)C.[NH4+].[BH4-].[Na+]>O.C(O)(=O)C>[N+:15]([CH2:18][CH2:10][C:9]1[CH:8]=[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH:14]=[CH:13][CH:12]=1)([O-:17])=[O:16]

Participants

7

Reactant 4

HCID 6375NitromethaneHCID 517165Ammonium AcetateHCID 37100393-(Pyridin-2-yl)benzaldehydeHCID 4311764Sodium borohydride

Product 1

HCID 592551612-(3-(2-Nitro-ethyl)-phenyl)-pyridineYield 71.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To a mixture of 3-pyridin-2-yl-benzaldehyde (290 mg, 1.6 mmol) described in Manufacturing Example 84-1-1 and acetic acid (5 mL) were added nitromethane (0.65 mL, 12 mmol) and ammonium acetate (370 mg, 4.8 mmol), which was stirred for 2 hours at 100° C. The reaction mixture was cooled to room temperature and water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. A mixture of dimethyl sulfoxide (6 mL) and acetic acid (0.4 mL) was added to the resulting residue, and sodium borohydride (97 mg, 2.6 mmol) was added at room temperature while cooling appropriately. The reaction mixture was stirred for 10 minutes at the same temperature. Water was added to the reaction mixture at room temperature, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The resulting residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (260 mg, 71%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under a reduced pressure
  6. additionA mixture of dimethyl sulfoxide (6 mL) and acetic acid (0.4 mL)
  7. additionwas added at room temperature
  8. temperaturewhile cooling appropriately
  9. stirringThe reaction mixture was stirred for 10 minutes at the same temperature
  10. extractionwhich was then extracted with ethyl acetate
  11. washThe organic layer was washed with saturated aqueous sodium chloride
  12. concentrationwas concentrated under a reduced pressure
  13. customThe resulting residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-3809bb5a9f8c46d4b39ff2bcaaa24707
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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