Acetic Acid → HCID 10523682, compound

HRID 1736190Notes

Reaction equation

HRID 1736190 reaction equation
[F:1][C:2]1[C:3]([CH2:35][OH:36])=[C:4]([F:34])[C:5]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([NH:17]C(=O)C(C)(C)C)=[C:13]([F:24])[CH:12]=3)=[CH:8][C:7](=[O:25])[C:6]=2[C:26]=1[NH:27]C(=O)C(C)(C)C.[C:37](O)(=[O:39])[CH3:38]>S(=O)(=O)(O)O>[C:37]([O:36][CH2:35][C:3]1[C:2]([F:1])=[C:26]([NH2:27])[C:6]2[C:7](=[O:25])[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([F:24])[CH:12]=3)[O:10][C:5]=2[C:4]=1[F:34])(=[O:39])[CH3:38]

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 10673123HCID 10673123, compound

Product 1

HCID 10523682HCID 10523682, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
100 °C

Procedure

6.02 g (11.9 mmol) of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-hydroxymethyl-5-pivaloylamino-4H-1-benzopyran-4-one obtained in Example 118 (4) was dissolved in a mixed solvent of 160 mL of acetic acid and 40 mL of concentrated sulfuric acid and the solution was stirred at 100° C. for 35 minutes. The reaction solution was cooled on ice, poured into ice water and the mixture was extracted twice 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, the residue was purified by silica gel column chromatography (chloroform:methanol=100:1) and recrystallized from chloroform/methanol/n=hexane to give 2.43 g of Compound 123 (yield: 54%).

Workup

  1. temperatureThe reaction solution was cooled on ice
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. 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
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (chloroform:methanol=100:1)
  7. customrecrystallized from chloroform/methanol/n=hexane

Sources & evidence

ORD record
ord-f2d5eccb40b844d1a6c677d51cfba307
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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