Hydrogen Peroxide → 2-Amino-4-fluoro-3-methoxy-6-methylbenzoic Acid

HRID 17288Notes

Reaction equation

HRID 17288 reaction equation
OO.[O:3]1CCOCC1.[F:9][C:10]1[C:18]([O:19][CH3:20])=[C:17]2[C:13]([C:14](=[O:22])C(=O)[NH:16]2)=[C:12]([CH3:23])[CH:11]=1.[OH-].[Na+]>O>[NH2:16][C:17]1[C:18]([O:19][CH3:20])=[C:10]([F:9])[CH:11]=[C:12]([CH3:23])[C:13]=1[C:14]([OH:22])=[O:3]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 68585022HCID 68585022, compound

Product 1

HCID 860974152-Amino-4-fluoro-3-methoxy-6-methylbenzoic Acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

With cooling with ice, a solution of 30% aqueous hydrogen peroxide (6.3 ml, 61.5 mmol) diluted with water (8.2 ml) was added to a dioxane (50 ml) solution of 6-fluoro-7-methoxy-4-methyl-1H-indole-2,3-dione (I-28) (2.57 g), at the same temperature, a water (230 ml) solution of sodium hydroxide (6.15 g, 153.8 mmol) was dropwise added, taking 1 hour, followed by stirring for 4 hours with gradually heating up to room temperature. The reaction liquid was washed twice with chloroform, acetic acid was added to the aqueous layer followed by controlling at pH of 3 to 4 and extraction three times with ethyl acetate, the organic layer was washed twice with saturated brine, then dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the resulting residue was subjected to column chromatography, and the eluate with chloroform alone was concentrated under reduced pressure to obtain the entitled compound (1.54 g, 28% from I-30) as a yellow solid.

Workup

  1. temperatureWith cooling with ice
  2. customThe reaction liquid
  3. washwas washed twice with chloroform, acetic acid
  4. additionwas added to the aqueous layer
  5. extractionby controlling at pH of 3 to 4 and extraction three times with ethyl acetate
  6. washthe organic layer was washed twice with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationAfter filtration and concentration under reduced pressure
  9. concentrationthe eluate with chloroform alone was concentrated under reduced pressure
  10. customto obtain the entitled compound (1.54 g, 28% from I-30) as a yellow solid

Sources & evidence

ORD record
ord-bc302860e9b84c6eb2c4bcb1c2f5cb62
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

Loading…