Potassium Iodide → HCID 21938638, compound

HRID 1280843Notes

Reaction equation

HRID 1280843 reaction equation
[CH2:1]([C:3]1[CH:4]=[CH:5][C:6](N)=[C:7]([CH2:9][C:10]([OH:12])=[O:11])[CH:8]=1)[CH3:2].N([O-])=O.[Na+].[I-:18].[K+]>O.Cl>[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([I:18])=[C:7]([CH2:9][C:10]([OH:12])=[O:11])[CH:8]=1)[CH3:2]

Participants

6

Reactant 3

HCID 4875Potassium IodideHCID 21938641HCID 21938641, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 21938638HCID 21938638, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent3×

Procedure

5-Ethyloxindole (˜54 g, ˜335 mmol), ethanol (750 ml), water (150 ml) and potassium hydroxide (65 g, 1.62 mol) are combined and heated at reflux for 3 days. The mixture is allowed to cool and then filtered through a bed of Celite. The filtrate is concentrated under reduced pressure, water is added and the pH adjusted to 6.5. The precipitate is filtered off, washed with water and dried in an oven overnight to yield 5-ethyl-2-aminophenylacetic acid. A mixture of water (405 ml) and concentrated HCl (48 ml) is stirred and cooled to 0°. 5-Ethyl-2-aminophenylacetic acid (53.7 g, 300 mmol) is slowly added while maintaining the temperature at 0-2°. After this addition a solution of sodium nitrite (22.2 g, 322 mmol) in 60 ml water is added dropwise over 30 minutes keeping the temperature at 0-2°. After a further 20 minutes a solution of potassium iodide (48 g, 290 mmol) in 18 ml conc HCl and 130 ml water is added dropwise while keeping the temperature below 10° C. The reaction mixture is allowed to warm to room temperature and then heated to reflux for 2 hours. The mixture is extracted with ethyl acetate and ether (1:1 mixture, 4×300 ml), the organic layer is then washed first with a 30% aqueous solution of sodium thiosulfite and then with a sodium hydroxide solution (0.1 M) before being acidified to pH 6 and extracted with ethyl acetate. This solution is washed with saturated brine, dried (magnesium sulfate), filtered, and the solvent removed under reduced pressure. The residue is treated with hexane to yield 5-ethyl-2-iodophenylacetic acid.

Workup

  1. temperaturecooled to 0°
  2. temperaturewhile maintaining the temperature at 0-2°
  3. additionis added dropwise over 30 minutes
  4. customat 0-2°
  5. customthe temperature below 10° C
  6. temperatureheated
  7. temperatureto reflux for 2 hours
  8. extractionThe mixture is extracted with ethyl acetate and ether (1:1 mixture, 4×300 ml)
  9. washthe organic layer is then washed first with a 30% aqueous solution of sodium thiosulfite
  10. extractionextracted with ethyl acetate
  11. washThis solution is washed with saturated brine
  12. dry with materialdried (magnesium sulfate)
  13. filtrationfiltered
  14. customthe solvent removed under reduced pressure
  15. additionThe residue is treated with hexane

Sources & evidence

ORD record
ord-83e7eb90e30b428faff32317d2c99949
Source dataset
uspto-grants-2002_09
Patent number
US06451858B2

Reaction notes

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