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

HRID 570518Notes

Reaction equation

HRID 570518 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 were dissolved in 100 ml of DMF, 30.304 g (93.01 mmol) of caesium carbonate and 16.116 g (85.26 mmol) of 2-fluorobenzyl bromide were added, and the mixture was stirred at RT overnight. The mixture was concentrated and taken up in dichloromethane, and water was added. The organic phase was removed and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, filtered through a silicone filter and concentrated. The residue was purified by flash chromatography on silica gel (eluent: hexane/ethyl acetate, gradient). 11.37 g (60% of theory) of the target compound were obtained.

Workup

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

Sources & evidence

ORD record
ord-143f6f879a1448ba8fe0902f03a5d181
Source dataset
uspto-grants-2015_05
Patent number
US09023849B2

Reaction notes

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