Dimethyl Sulfate → Methyl 5-iodo-2-methoxybenzoate

HRID 908305Notes

Reaction equation

HRID 908305 reaction equation
[I:1][C:2]1[CH:3]=[CH:4][C:5](O)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[C:12]([O-])([O-])=O.[K+].[K+].COS([O:23][CH3:24])(=O)=O>CC(C)=O.O>[I:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][CH3:24])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:12])=[O:8]

Participants

6

Reactant 3

HCID 6497Dimethyl SulfateHCID 83885-Iodosalicylic acidHCID 11430Potassium Carbonate

Product 1

HCID 11011762Methyl 5-iodo-2-methoxybenzoateYield 99.5%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

5-iodo-2-hydroxybenzoic acid (2.81 g, 10.6 mmol) was suspended in acetone (50 ml) and K2CO3 (6.77 g, 49.0 mmol) was added. The reaction was cooled in an ice water bath, and dimethylsulfate (2.4 ml, 25 mmol) was added via syringe. The reaction was warmed to room temperature, then heated to reflux, and stirred overnight. After 14.75 hours, the reaction was cooled to room temperature, diluted with water (150 ml), and stirred for 30 minutes. It was then extracted with EtOAc (3×50 ml), and the organic extracts were combined, dried over magnesium sulfate, filtered, concentrated, and purified on silica gel (Biotage instrument, 5% EtOAc/hexanes->100% EtOAc) to give methyl 5-iodo-2-methoxybenzoate (3.08 g, 99%).

Workup

  1. temperatureThe reaction was cooled in an ice water bath
  2. temperatureheated
  3. temperatureto reflux
  4. waitAfter 14.75 hours
  5. temperaturethe reaction was cooled to room temperature
  6. stirringstirred for 30 minutes
  7. extractionIt was then extracted with EtOAc (3×50 ml)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified on silica gel (Biotage instrument, 5% EtOAc/hexanes->100% EtOAc)

Sources & evidence

ORD record
ord-35f873cd779b4f6f84c7e60ddaef0904
Source dataset
uspto-grants-2011_09
Patent number
US08017601B2

Reaction notes

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