Methyl iodide → 3-Fluoro-4-nitroanisole

HRID 2182903Notes

Reaction equation

HRID 2182903 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].N12CCCN=C1CCCC[CH2:13]2.IC>CC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([O:11][CH3:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 5209483-Fluoro-4-nitrophenol

Product 1

HCID 5656543-Fluoro-4-nitroanisoleYield 88%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 3-fluoro-4-nitrophenol (75 g, 0.48 mol) in acetone (700 mL) was cooled in an ice-water bath. 1,8-Diazabicyclo[5,4,0]undec-7-ene (145 g, 0.96 mol) was then added over ca. 5 min. Finally, iodomethane (135 g, 0.96 mol) was added over 10 min. The mixture was stirred at room temperature for 16 hr. Additional 1,8-diazabicyclo[5,4,0]undec-7-ene (73 g, 0.48 mol) and iodomethane (68 g, 0.48 mol) were added, and the mixture was warmed to 50° C. for 1 hr. After a solid was removed by filtration, the concentrated filtrate was mixed with ethyl acetate and 1 M hydrochloric acid. The organic layer was washed with additional hydrochloric acid and aqueous sodium bicarbonate, concentrated, and stirred in 1% ethyl acetate in hexanes. The resulting solid was collected and dried to give 72 g (88%) of the title compound.

Workup

  1. temperaturethe mixture was warmed to 50° C. for 1 hr
  2. customAfter a solid was removed by filtration
  3. additionthe concentrated filtrate was mixed with ethyl acetate and 1 M hydrochloric acid
  4. washThe organic layer was washed with additional hydrochloric acid and aqueous sodium bicarbonate
  5. concentrationconcentrated
  6. stirringstirred in 1% ethyl acetate in hexanes
  7. customThe resulting solid was collected
  8. customdried

Sources & evidence

ORD record
ord-92218fe4598b4d48aac538780f13a1f2
Source dataset
uspto-grants-2005_05
Patent number
US06897227B2

Reaction notes

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