Phenol → HCID 21912879, compound

HRID 1352603Notes

Reaction equation

HRID 1352603 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][O:23][CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)[C:14]([CH3:31])=[C:13]([CH3:32])[N:12]=1>COCCOCCOC.C(OCC)(=O)C>[CH3:32][C:13]1[C:14]([CH3:31])=[C:15]([NH:20][CH2:21][CH2:22][O:23][CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)[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

6

Reactant 3

HCID 996Phenol2×HCID 24758Sodium hydride2×HCID 21913198HCID 21913198, compound

Product 1

HCID 21912879HCID 21912879, compoundYield 20.8%

Reagents, catalysts & solvents 2

HCID 8150DiglymeSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

Under a nitrogen atmosphere, diglyme (25 mL) was added to sodium hydride (1.81 g, 45.2 mmol), which is available as a 60% dispersion in mineral oil, and the mixture was cooled to 5° C. A solution of phenol (4.54 g, 48.2 mmol) in diglyme (50 mL) was added dropwise over a period of 15 minutes. The reaction became homogeneous after 15 minutes. A solution of (2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)-[2-(pyridin-4-ylmethoxy)ethyl]amine (10.15 g, 30.14 mmol) was added, and the reaction was heated at 160° C. for 13 hours. An analysis by HPLC indicated the presence of starting material. Additional phenol (3.12 g, 33.2 mmol) was added to 60% sodium hydride (1.24 g, 31.1 mmol) in diglyme, and the mixture was stirred until it became homogeneous. This solution was added to the cooled reaction flask, and the reaction was heated at 160° C. for 9.5 hours. The reaction was allowed to cool to room temperature, and the volatiles were removed under reduced pressure to provide a black oil. The oil was dissolved in ethyl acetate, and the solution was washed with 1 N potassium hydroxide (3×) and brine (3×), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 80:20 ethyl acetate:hexane) to provide 2.47 g of (2,3-dimethyl-5-nitro-6-phenoxypyridin-4-yl)-[2-(pyridin-4-ylmethoxy)ethyl]amine.

Workup

  1. temperaturethe reaction was heated at 160° C. for 13 hours
  2. additionThis solution was added to the cooled reaction flask
  3. temperaturethe reaction was heated at 160° C. for 9.5 hours
  4. temperatureto cool to room temperature
  5. customthe volatiles were removed under reduced pressure
  6. customto provide a black oil
  7. washthe solution was washed with 1 N potassium hydroxide (3×) and brine (3×)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by column chromatography on silica gel (eluting with 80:20 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-221e63204fc0425197241d13426e463b
Source dataset
uspto-grants-2007_05
Patent number
US07220758B2

Reaction notes

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