Nitromethane → HCID 59255228, compound

HRID 640214Notes

Reaction equation

HRID 640214 reaction equation
[O:1]([CH2:8][C:9]1[N:14]=[CH:13][C:12]([CH:15]=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O-].[Li+].[N+:20]([CH3:23])([O-:22])=[O:21].C(OC(=O)C)(=O)C.C(N(CC)CC)C.[BH4-].[Na+]>O.CO.C(OCC)(=O)C>[N+:20]([CH2:23][CH2:15][C:12]1[CH:11]=[CH:10][C:9]([CH2:8][O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[N:14][CH:13]=1)([O-:22])=[O:21]

Participants

10

Reactant 6

HCID 6375NitromethaneHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 4177230Lithium methanolate2×HCID 4311764Sodium borohydrideHCID 59255289HCID 59255289, compound

Product 1

HCID 59255228HCID 59255228, compoundYield 14.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a methanol (20.0 mL) solution of 6-phenoxymethyl-pyridine-3-carbaldehyde (1.00 g, 4.69 mmol) described in Manufacturing Example 54-1-4 was added lithium methoxide (21.4 mg, 0.56 mmol) under nitrogen atmosphere at room temperature. This was cooled to 0° C., and nitromethane (372 mg, 6.10 mmol) and lithium methoxide (193 mg, 5.07 mmol) were added and stirred for 10 minutes at room temperature. The reaction solution was then concentrated under a reduced pressure. Tetrahydrofuran (20.0 mL) was added to the residue, and then acetic anhydride (6.24 g, 61.1 mmol) and triethylamine (1.42 mL, 10.2 mmol) were added and stirred for 1 hour at 70° C. Water and ethyl acetate were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. This organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated from the filtrate under a reduced pressure. Methanol (20.0 mL) was added to the residue, and sodium borohydride (263 mg, 6.96 mmol) was then added on an ice bath (0° C.). Following 5 minutes of stirring at 0° C., water was added dropwise at 0° C. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated from the filtrate under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:1) to obtain the title compound (170 mg, 14.2%).

Workup

  1. concentrationThe reaction solution was then concentrated under a reduced pressure
  2. additionTetrahydrofuran (20.0 mL) was added to the residue
  3. stirringstirred for 1 hour at 70° C
  4. extractionthe organic layer was extracted with ethyl acetate
  5. washThis organic layer was washed with water and saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe solvent was evaporated from the filtrate under a reduced pressure
  9. additionwas then added on an ice bath (0° C.)
  10. waitFollowing 5 minutes
  11. stirringof stirring at 0° C.
  12. extractionThe reaction mixture was extracted with ethyl acetate
  13. washthe organic layer was washed with water and saturated aqueous sodium chloride
  14. dry with materialdried over anhydrous magnesium sulfate
  15. filtrationfiltered
  16. customThe solvent was evaporated from the filtrate under a reduced pressure
  17. customthe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:1)

Sources & evidence

ORD record
ord-f6ea0955706943b1b769db19af6a6234
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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