Phenol → HCID 21913299, compound

HRID 1352616Notes

Reaction equation

HRID 1352616 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[C:15]([NH:20][CH2:21][CH2:22][CH2:23][OH:24])[C:14]([CH3:25])=[C:13]([CH3:26])[N:12]=1>O1CCCC1>[CH3:26][C:13]1[C:14]([CH3:25])=[C:15]([NH:20][CH2:21][CH2:22][CH2:23][OH:24])[C:16]([N+:17]([O-:19])=[O:18])=[C:11]([O:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:12]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 21913176HCID 21913176, compound

Product 1

HCID 21913299HCID 21913299, compoundYield 55.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (7.80 g of a 60% dispersion in mineral oil, 195 mmol) was added in portions to a chilled (0° C.) solution of phenol (18.36 g, 195 mmol) in tetrahydrofuran (200 mL). After the addition was completed the reaction mixture was allowed to stir at ambient temperature for 30 minutes. Solid 3-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]propan-1-ol (16.89 g, 65.0 mmol) was added and the reaction mixture was heated at reflux for 5 days. The reaction mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate (400 mL) and water (100 mL). The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and then concentrated under reduced pressure. The residue was purified by flash chromatography (500 mL silica gel eluting with a gradient of 30–75% ethyl acetate in hexanes) and then heated under high vacuum until it melted. The melt solidified to provide 11.54 g of 3-[(2,3-dimethyl-5-nitro-6-phenoxypyridin-4-yl)amino]propan-1-ol.

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux for 5 days
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customThe residue was partitioned between ethyl acetate (400 mL) and water (100 mL)
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash chromatography (500 mL silica gel eluting with a gradient of 30–75% ethyl acetate in hexanes) and
  12. temperaturethen heated under high vacuum until it

Sources & evidence

ORD record
ord-4dc47571a74943a698d64533374b91a4
Source dataset
uspto-grants-2007_05
Patent number
US07220758B2

Reaction notes

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