Nitromethane → HCID 59255440, compound

HRID 78149Notes

Reaction equation

HRID 78149 reaction equation
[F:1][C:2]1[C:3]([O:8][CH2:9][C:10]2[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[N+:18]([CH3:21])([O-:20])=[O:19].C([O-])(=O)C.[NH4+].[BH4-].[Na+].C(=O)([O-])O.[Na+]>CS(C)=O.O.C(O)(=O)C>[F:1][C:2]1[C:3]([O:8][CH2:9][C:10]2[CH:17]=[CH:16][C:13]([CH2:14][CH2:21][N+:18]([O-:20])=[O:19])=[CH:12][CH:11]=2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 6375NitromethaneHCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 4311764Sodium borohydrideHCID 592552614-(3-Fluoro-pyridin-2-yloxymethyl)-benzaldehyde

Product 1

HCID 59255440HCID 59255440, compoundYield 64%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To an acetic acid (20 mL) solution of 4-(3-fluoro-pyridin-2-yloxymethyl)-benzaldehyde (887 mg, 3.84 mmol) described in Manufacturing Example 149-1-2 were added nitromethane (1.04 mL, 19.2 mmol) and ammonium acetate (592 mg, 7.68 mmol), which was stirred under nitrogen atmosphere for 4 hours and 30 minutes at 100° C. Water was added to the reaction mixture at 0° C., 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 filtrated was concentrated under a reduced pressure. To a solution of this residue in dimethyl sulfoxide (20 mL) and acetic acid (1 mL) was added sodium borohydride (291 mg, 7.68 mmol), which was stirred for 30 minutes at room temperature. Sodium hydrogencarbonate and water were added to the reaction solution at room temperature while cooling appropriately, 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 NH silica gel column chromatography (heptane: ethyl acetate=2:1) to obtain the title compound (674 mg, 64%).

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 filtrated was concentrated under a reduced pressure
  7. stirringwas stirred for 30 minutes at room temperature
  8. temperaturewhile cooling appropriately
  9. extractionwhich was extracted with ethyl acetate
  10. customThe organic layer was separated
  11. washwashed with water and 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=2:1)

Sources & evidence

ORD record
ord-8cd026690b82471caa06809eaf1b7c15
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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