Dimethyl Sulfate → 5-Fluoro-2-nitroanisole

HRID 1171021Notes

Reaction equation

HRID 1171021 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([OH:8])[CH:7]=1.[C:12](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>CC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([O:8][CH3:12])[CH:7]=1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 99375-Fluoro-2-nitrophenolHCID 11430Potassium Carbonate

Product 1

HCID 27792505-Fluoro-2-nitroanisoleYield 100%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 5-fluoro-2-nitrophenol (3.0 g, 19.1 mmol), potassium carbonate (2.50 g, 21.0 mmol) and dimethyl sulfate (2.65 g, 21.0 mmol) in acetone was stirred at ambient temperature for 24 hours. The solvents were removed under reduced pressure and then water (30 mL) and dichloromethane (30 mL) was added to the residue. The combined organics solutions were dried over magnesium sulfate then filtered and the filtrate concentrated under reduced pressure to provide an oil. This was purified by flash chromatography on silica gel using dichloromethane/heptane (7:3) as an eluent to provide the title compound as a crystalline solid (3.24 g, 100%): 1H NMR (CDCl3, 400 MHz) δ 7.96 (M, 1H), 6.80 (m, 1H), 6.73 (m, 1H), 3.96 (s, 3H); RP-HPLC (Hypersil HS C18, 5 μm, 100 A, 250×4.6 mm; 5%-100% acetonitrile-0.05 M ammonium acetate over 25 min, 1 μL/min) tr 17.82 min; MS: MH+ 172.2

Workup

  1. customThe solvents were removed under reduced pressure
  2. additionwater (30 mL) and dichloromethane (30 mL) was added to the residue
  3. dry with materialThe combined organics solutions were dried over magnesium sulfate
  4. filtrationthen filtered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customto provide an oil
  7. customThis was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-e3aafd9cdc0640049b12ff6d9616f4e8
Source dataset
uspto-grants-2010_11
Patent number
US07829570B2

Reaction notes

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