Water → HCID 23238913, compound

HRID 1736226Notes

Reaction equation

HRID 1736226 reaction equation
[F:1][C:2]1[C:3]([CH2:35]OS(C)(=O)=O)=[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].[CH3:41][N:42]([CH3:46])[CH2:43][CH2:44][OH:45].[H-].[Na+].O>CN(C)C=O>[CH3:41][N:42]([CH3:46])[CH2:43][CH2:44][O:45][CH2:35][C:3]1[C:2]([F:1])=[C:26]([NH:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])[C:6]2[C:7](=[O:25])[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:20])[CH3:21])=[C:13]([F:24])[CH:12]=3)[O:10][C:5]=2[C:4]=1[F:34]

Participants

6

Reactant 4

HCID 962WaterHCID 79022-(Dimethylamino)ethanolHCID 24758Sodium hydrideHCID 10721996HCID 10721996, compound

Product 1

HCID 23238913HCID 23238913, compoundYield 60.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

800 mg (1.37 mmol) of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methanesulfonyloxymethyl-5-pivaloylamino-4H-1-benzopyran-4-one obtained in EXAMPLE 120 (1) was dissolved in 20 mL of dimethylformamide at 0° C., 0.28 mL (2.75 mmol) of 2-dimethylaminoethanol and 220 mg (5.20 mmol) of sodium hydride (60% oil dispersion) were added, and the mixture was stirred at room temperature for 80 minutes. Water was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=9:1) to give 477 mg of 7-(2-dimethylaminoethoxymethyl)-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-pivaloylamino-4H-1-benzopyran-4-one (yield: 60%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (chloroform:methanol=9:1)

Sources & evidence

ORD record
ord-fdb4583a3d494af2bd67082471a49edc
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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