Methyl iodide → HCID 10601598, compound

HRID 1736157Notes

Reaction equation

HRID 1736157 reaction equation
[F:1][C:2]1[C:3]([OH:35])=[C:4]([F:34])[C:5]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[C:13]([F:24])[CH:12]=3)=[CH:8][C:7](=[O:25])[C:6]=2[C:26]=1[NH:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30].[C:36](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O>[F:1][C:2]1[C:3]([O:35][CH3:36])=[C:4]([F:34])[C:5]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[C:13]([F:24])[CH:12]=3)=[CH:8][C:7](=[O:25])[C:6]=2[C:26]=1[NH:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 10719858HCID 10719858, compound

Product 1

HCID 10601598HCID 10601598, compoundYield 78.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

348 mg (0.710 mmol) of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl )-7-hydroxy-5-pivaloylamino-4H-1-benzopyran-4-one obtained in Example 86 (3) was dissolved in 35 mL of acetone, 166 mg (1.20 mmol) of potassium carbonate and 0.45 mL (7.1 mmol) of iodomethane were added and the mixture was heated at reflux for 40 minutes. The reaction solution was filtered, the filtrate was concentrated, water was added to the residue and the mixture was extracted once with ethyl acetate. The organic layer was washed twice with a 1N aqueous solution of sodium hydroxide, once with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (chloroform) to give 280 mg of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methoxy-5-pivaloylamino-4H-1-benzopyran-4-one (yield: 78%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 40 minutes
  3. filtrationThe reaction solution was filtered
  4. concentrationthe filtrate was concentrated
  5. additionwater was added to the residue
  6. extractionthe mixture was extracted once with ethyl acetate
  7. washThe organic layer was washed twice with a 1N aqueous solution of sodium hydroxide, once with water and once with an aqueous saturated solution of sodium chloride
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationThe solvent was distilled off under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (chloroform)

Sources & evidence

ORD record
ord-a8a9d45b93df4a7db7ea80bf6b039c42
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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