Ethyl bromoacetate → HCID 19434994, compound

HRID 1736220Notes

Reaction equation

HRID 1736220 reaction equation
[NH2:1][C:2]1[C:7]2[C:8](=[O:26])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14]([F:25])[CH:13]=3)[O:11][C:6]=2[C:5]([F:27])=[CH:4][C:3]=1[F:28].Br[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>CN(C)C=O>[CH2:34]([O:33][C:31]([CH2:30][NH:1][C:2]1[C:7]2[C:8](=[O:26])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:14]([F:25])[CH:13]=3)[O:11][C:6]=2[C:5]([F:27])=[CH:4][C:3]=1[F:28])=[O:32])[CH3:35]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 19434934HCID 19434934, compound

Product 1

HCID 19434994HCID 19434994, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

1.02 g (2.62mmol) of 5-amino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one obtained in Example 66 was dissolved in 30 mL of dimethylformamide under argon atmosphere, 5.8 mL (52.3 mmol) of ethyl bromoacetate and 1.80 g (13.1 mmol) of potassium carbonate were added and the mixture was stirred at 100° C. for 21 hours. The reaction solution was cooled on ice, an aqueous saturated solution of ammonium chloride was added and the precipitated crystals were collected by filtration. The mother liquor was extracted with ethyl acetate, and the organic layer was washed with water and with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the residue was added to the above crystals and the mixture was purified by silica gel column chromatography (chloroform:acetonitrile=25:1) to give 824 mg of 5-ethoxycarbonylmethylamino-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-4H-1-benzopyran-4-one (yield: 66%).

Workup

  1. temperatureThe reaction solution was cooled on ice
  2. filtrationthe precipitated crystals were collected by filtration
  3. extractionThe mother liquor was extracted with ethyl acetate
  4. washthe organic layer was washed with water and with an aqueous saturated solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. additionthe residue was added to the above crystals
  8. customthe mixture was purified by silica gel column chromatography (chloroform:acetonitrile=25:1)

Sources & evidence

ORD record
ord-fd75c2bec14040f7ae986dafbff970c8
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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