Phenol → HCID 66814468, compound

HRID 1097575Notes

Reaction equation

HRID 1097575 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](CC(C)C)[C:14]([CH3:24])=[C:13]([CH3:25])[N:12]=1>O1CCCC1>[CH3:24][C:14]1[C:15]([NH:12][CH2:13][CH:14]([CH3:24])[CH3:15])=[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][C:13]=1[CH3:25]

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 86626289HCID 86626289, compound

Product 1

HCID 66814468HCID 66814468, compoundYield 216.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Sodium hydride (19.8 g of a 60% dispersion in mineral oil, 0.495 mol) in tetrahydrofuran (THF) (450 mL) was cooled to 0° C.; a solution of phenol (77.7 g, 0.826 mol) in THF (150 mL) was added slowly over a period of 30 minutes. The reaction was stirred at ambient temperature for 30 minutes, and a solution of 2-chloro-5,6-dimethyl-4-(2-methylpropyl)-3-nitropyridine (60.78 g, 0.236 mol) in THF (350 mL) was added. The reaction was heated to 70° C., heated at 50° C. overnight, allowed to cool to ambient temperature, and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (800 mL). The resulting solution was washed sequentially with 1 N aqueous sodium hydroxide (1×800 mL), brine (3×400 mL), 1 N aqueous sodium hydroxide (1×400 mL), brine (1×400 mL), 1 N aqueous sodium hydroxide (1×400 mL), and deionized water (1×400 mL); dried over magnesium sulfate; filtered through a layer of CELITE filter agent; concentrated under reduced pressure; and further dried overnight under high vacuum to provide 80.46 g of 5,6-dimethyl-N-(2-methylpropyl)-3-nitro-2-phenoxypyridin-4-amine as an orange-red solid containing some mineral oil.

Workup

  1. temperatureThe reaction was heated to 70° C.
  2. temperatureheated at 50° C. overnight
  3. temperatureto cool to ambient temperature
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate (800 mL)
  6. washThe resulting solution was washed sequentially with 1 N aqueous sodium hydroxide (1×800 mL), brine (3×400 mL), 1 N aqueous sodium hydroxide (1×400 mL), brine (1×400 mL), 1 N aqueous sodium hydroxide (1×400 mL), and deionized water (1×400 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered through a layer of CELITE filter agent
  9. concentrationconcentrated under reduced pressure
  10. customand further dried overnight under high vacuum

Sources & evidence

ORD record
ord-208f9b25045e4a00b0ae405c17ef0c43
Source dataset
uspto-grants-2012_03
Patent number
US08143270B2

Reaction notes

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