4-Methoxyphenol → 4-(4-Methoxy-phenoxy)-3,5-dimethyl-nitrobenzene

HRID 1359158Notes

Reaction equation

HRID 1359158 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.Cl[C:13]1[C:18]([CH3:19])=[CH:17][C:16]([N+:20]([O-:22])=[O:21])=[CH:15][C:14]=1[CH3:23]>CN1CCCC1=O>[CH3:23][C:14]1[CH:15]=[C:16]([N+:20]([O-:22])=[O:21])[CH:17]=[C:18]([CH3:19])[C:13]=1[O:11][C:8]1[CH:9]=[CH:10][C:5]([O:4][CH3:3])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 90154-MethoxyphenolHCID 24758Sodium hydrideHCID 99205692-Chloro-1,3-dimethyl-5-nitrobenzene

Product 1

HCID 100846724-(4-Methoxy-phenoxy)-3,5-dimethyl-nitrobenzene

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride (NaH; 60% dispersion in mineral oil; 64.11 g, 1.603 mol) in 350 mL of N-methylpyrrolidone (NMP) is cooled to 0° C. and treated with a solution of 4-methoxyphenol (208.4 g, 1.679 mol) over 30 min. The mixture is warmed to room temperature (RT) and after 30 min, 4-chloro-3,5-dimethylnitrobenzene (283.2 g, 1.526 mol; prepared by the method described by Yokoyama et. al. in EP580550) is added in one portion and the reaction is heated at 120° C. for 2 h. The reaction is cooled to room temperature (RT) and quenched with water (1500 mL). The suspension is cooled to 0° C., stirred for 30 min, then filtered and the filtercake is washed with water and dried in vacuo. The crude product, ethyl acetate (EtOAc; 2100 mL) and charcoal (42.6 g) were heated to reflux and the solids were removed by filtration through celite while hot. The filtrate is concentrated under reduced pressure to ca. 800 mL and the resulting suspension is cooled to 0° C. and stirred for 30 min. The product is collected by vacuum filtration, washed with cold EtOAc and dried in vacuo to afford 3,5-dimethyl-4-(4′-methoxyphenoxy)nitrobenzene: NMR (CDCl3) 2.22 (s, 6H), 3.78 (s, 3H), 6.68 (d, 2H, J=8.7), 6.82 (d, 2H, J=8.7), 8.02 (s, 2H).

Workup

  1. temperatureThe mixture is warmed to room temperature (RT)
  2. customprepared by the method
  3. additionis added in one portion
  4. temperaturethe reaction is heated at 120° C. for 2 h
  5. temperatureThe reaction is cooled to room temperature (RT)
  6. customquenched with water (1500 mL)
  7. temperatureThe suspension is cooled to 0° C.
  8. filtrationfiltered
  9. washthe filtercake is washed with water
  10. customdried in vacuo
  11. temperatureThe crude product, ethyl acetate (EtOAc; 2100 mL) and charcoal (42.6 g) were heated
  12. temperatureto reflux
  13. customthe solids were removed by filtration through celite while hot
  14. concentrationThe filtrate is concentrated under reduced pressure to ca. 800 mL
  15. temperaturethe resulting suspension is cooled to 0° C.
  16. stirringstirred for 30 min
  17. filtrationThe product is collected by vacuum filtration
  18. washwashed with cold EtOAc
  19. customdried in vacuo

Sources & evidence

ORD record
ord-69065ef9043c4eb399115706db2e3913
Source dataset
uspto-grants-2003_07
Patent number
US06599942B1

Reaction notes

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