Water → HCID 21018333, compound

HRID 1744581Notes

Reaction equation

HRID 1744581 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([NH:15][C:16]([C:18]2[N:19]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH:20]=[CH:21][CH:22]=2)=[O:17])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])#[N:2].[H-].[Na+].Br[CH2:33][C:34]([O:36]CC)=[O:35].O>CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([N:15]([C:16]([C:18]2[N:19]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH:20]=[CH:21][CH:22]=2)=[O:17])[CH2:33][C:34]([OH:36])=[O:35])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])#[N:2]

Participants

6

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 22228181HCID 22228181, compound

Product 1

HCID 21018333HCID 21018333, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-[3-Cyano-4-neopentyloxyphenyl]-1-(4-fluorophenyl) pyrrole-2-carboxamide (4.0 g) and sodium hydride (60% content, 0.6 g) were reacted in dimethylformamide (40 ml) under ice-cooling for 1 h. Dimethylformamide solution (3 ml) containing ethyl bromoacetate (3.4g) was added and the mixture was stirred under ice-cooling for 1 h, and after allowed to warm to room temperature, stirred for another 1 h. The reaction mixture was added into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. To the residue were added ethanol (40 ml) and then 10% aqueous sodium hydroxide solution (50 ml). The mixture was stirred at a refluxing temperature for 30 min. The solvent was evaporated under reduced pressure. Dilute hydrochloric acid was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. A mixed solvent of chloroform-n-hexane was added to the residue to allow crystallization. The crystals were recrystallized from hydrous ethanol to give the title compound (3.0 g), melting point: 140–143° C.

Workup

  1. temperaturecooling for 1 h
  2. additionwas added
  3. temperaturecooling for 1 h
  4. stirringstirred for another 1 h
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customafter which the solvent was evaporated under reduced pressure
  9. additionTo the residue were added ethanol (40 ml)
  10. stirringThe mixture was stirred at a refluxing temperature for 30 min
  11. customThe solvent was evaporated under reduced pressure
  12. additionDilute hydrochloric acid was added to the residue
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe organic layer was washed with saturated brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. customafter which the solvent was evaporated under reduced pressure
  17. additionA mixed solvent of chloroform-n-hexane was added to the residue
  18. customcrystallization
  19. customThe crystals were recrystallized from hydrous ethanol

Sources & evidence

ORD record
ord-2beb727fc0684b0a8164bf5c9debe31a
Source dataset
uspto-grants-2006_03
Patent number
US07015218B1

Reaction notes

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