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

HRID 78005Notes

Reaction equation

HRID 78005 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][C:5]1[N:10]=[CH:9][C:8]([CH:11]=O)=[CH:7][CH:6]=1.[N+:17]([CH3:20])([O-:19])=[O:18].C([O-])(=O)C.[NH4+].[BH4-].[Na+]>O.C(O)(=O)C>[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:11][CH2:20][N+:17]([O-:19])=[O:18])=[CH:9][N:10]=1

Participants

7

Reactant 4

HCID 6375NitromethaneHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 592554196-(2-Fluoro-phenoxy)-pyridine-3-carbaldehyde

Product 1

HCID 592552802-(2-Fluoro-phenoxy)-5-(2-nitro-ethyl)-pyridineYield 61%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To a mixture of 6-(2-fluoro-phenoxy)-pyridine-3-carbaldehyde (210 mg, 0.97 mmol) described in Manufacturing Example 74-1-2 and acetic acid (3 mL) were added nitromethane (0.39 mL, 7.3 mmol) and ammonium acetate (220 mg, 2.9 mmol), which was stirred for 3 hours at 100° C. The reaction mixture was cooled to room temperature and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and was concentrated under a reduced pressure. A mixture of dimethyl sulfoxide (3 mL) and acetic acid (0.2 mL) was added to the resulting residue, and sodium borohydride (58 mg, 1.5 mmol) was added to the reaction mixture at room temperature while cooling appropriately. The reaction mixture was stirred for 10 minutes. Water was added to the reaction solution 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 residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (150 mg, 61%).

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. concentrationwas concentrated under a reduced pressure
  6. additionA mixture of dimethyl sulfoxide (3 mL) and acetic acid (0.2 mL)
  7. additionwas added to the reaction mixture at room temperature
  8. temperaturewhile cooling appropriately
  9. stirringThe reaction mixture was stirred for 10 minutes
  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 residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-afd5cf4eeb984913a61498c0712fad3f
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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