Cesium carbonate → HCID 178436885, compound

HRID 1671330Notes

Reaction equation

HRID 1671330 reaction equation
[CH2:1]([C:3]1[CH:4]=[C:5]([OH:8])[NH:6][N:7]=1)[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH:16]([CH3:27])[C:17]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=1[Cl:26])=[O:18]>CN(C=O)C>[Cl:26][C:20]1[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:19]=1[C:17](=[O:18])[CH:16]([O:8][C:5]1[NH:6][N:7]=[C:3]([CH2:1][CH3:2])[CH:4]=1)[CH3:27]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 109239912-Bromo-1-(2,4-dichlorophenyl)propan-1-oneHCID 178436956HCID 178436956, compound

Product 1

HCID 178436885HCID 178436885, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 5-ethyl-2H-pyrazol-3-ol (4.40 g, 39.2 mmol) in DMF (40 ml) is added cesium carbonate (13.42 g, 41.2 mmol) and the reaction mixture is heated to 50° C. After 5 minutes, 2-bromo-1-(2,4-dichloro-phenyl)-propan-1-one (Intermediate AA) (11.62 g, 41.2 mmol) in DMF (60 ml) is added slowly (addition time 10 minutes, initially yellow) and the reaction is stirred for a further 45 minutes giving a tan solution which is allowed to cool to RT. The reaction mixture is partitioned between EtOAc (150 ml) and 1N Na2CO3 (400 ml) and extracted with EtOAc (4×75 ml). The combined organic extracts are washed with H2O (1×200 ml) and brine (250 ml), dried (Na2SO4), filtered and concentrated in vacuo to yield a brown oil. The residue is pre-absorbed (dissolved in dichloromethane) onto silica gel and purified via Flashmaster (SiO2 340 g Snap cartridge column) eluting with 4:1 iso-hexane/EtOAc to 2:1 iso-hexane/EtOAc to yield the title compound as a pale yellow solid MS: m/z 313.12 [M+H]+

Workup

  1. additionaddition time 10 minutes
  2. customgiving a tan solution which
  3. temperatureto cool to RT
  4. customThe reaction mixture is partitioned between EtOAc (150 ml) and 1N Na2CO3 (400 ml)
  5. extractionextracted with EtOAc (4×75 ml)
  6. washThe combined organic extracts are washed with H2O (1×200 ml) and brine (250 ml)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield a brown oil
  11. customThe residue is pre-absorbed
  12. dissolution(dissolved in dichloromethane) onto silica gel
  13. custompurified via Flashmaster (SiO2 340 g Snap cartridge column)
  14. washeluting with 4:1 iso-hexane/EtOAc to 2:1 iso-hexane/EtOAc

Sources & evidence

ORD record
ord-c0b7dc6b5c134708822ed146b6ff16d4
Source dataset
uspto-grants-2011_08
Patent number
US07994203B2

Reaction notes

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