Cesium carbonate → 1-(2-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbonitrile

HRID 536486Notes

Reaction equation

HRID 536486 reaction equation
[NH:1]1[C:5]2[CH2:6][CH2:7][CH2:8][C:4]=2[C:3]([C:9]#[N:10])=[N:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20]Br>CN(C=O)C>[F:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20][N:1]1[C:5]2[CH2:6][CH2:7][CH2:8][C:4]=2[C:3]([C:9]#[N:10])=[N:2]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 67968alpha-Bromo-o-fluorotolueneHCID 231351391H,4H,5H,6H-cyclopenta[c]pyrazole-3-carbonitrile

Product 1

HCID 712853771-(2-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

10.320 g (77.50 mmol) of 1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbonitrile was dissolved in 100 ml DMF, 30.304 g (93.01 mmol) of caesium carbonate and 16.116 g (85.26 mmol) of 2-fluorobenzyl bromide were added and it was stirred at RT overnight. The reaction mixture was concentrated by evaporation and taken up in dichloromethane and water was added. The organic phase was separated and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, filtered on a silicone filter and concentrated by evaporation. The residue was purified by silica-gel flash chromatography (eluent: hexane/ethyl acetate, gradient). 11.37 g (60% of theor.) of the target compound was obtained.

Workup

  1. concentrationThe reaction mixture was concentrated by evaporation
  2. additionwater was added
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted twice with dichloromethane
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  6. filtrationfiltered on a silicone
  7. filtrationfilter
  8. concentrationconcentrated by evaporation
  9. customThe residue was purified by silica-gel flash chromatography (eluent: hexane/ethyl acetate, gradient)
  10. custom11.37 g (60% of theor.) of the target compound was obtained

Sources & evidence

ORD record
ord-03b9d815b3e743ea8922af16125b6382
Source dataset
uspto-grants-2014_10
Patent number
US08859569B2

Reaction notes

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