Benzyl Bromide → 2-Benzyl-2,4,5,6-tetrahydro-cyclopentapyrazole-3-carboxylic acid amide

HRID 475501Notes

Reaction equation

HRID 475501 reaction equation
[NH:1]1[C:5]2[CH2:6][CH2:7][CH2:8][C:4]=2[C:3]([C:9]([NH2:11])=[O:10])=[N:2]1.C([O-])([O-])=O.[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C.CCOC(C)=O>[CH2:18]([N:2]1[C:3]([C:9]([NH2:11])=[O:10])=[C:4]2[CH2:8][CH2:7][CH2:6][C:5]2=[N:1]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 451212581H,4H,5H,6H-cyclopenta[c]pyrazole-3-carboxamide

Product 1

HCID 587136472-Benzyl-2,4,5,6-tetrahydro-cyclopentapyrazole-3-carboxylic acid amideYield 18.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of 1,4,5,6-tetrahydro-cyclopentapyrazole-3-carboxylic acid amide (2.57 g, 17.0 mmol) in DMF (34 mL) at 25° C. was added K2CO3 (5.87 g, 42.5 mmol) followed by benzyl bromide (4.36 g g, 25.5 mmol). The reaction was stirred at ambient temperature for 16 h at which time the mixture was diluted with EtOAc (75 mL) and filtered. The filtrate was washed with H2O (100 mL) and the aqueous phase was back-extracted with EtOAc (75 mL) and CH2Cl2 (75 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography (50% EtOAc in hexanes gradient to 95% EtOAc in hexanes) gave 2-benzyl-2,4,5,6-tetrahydro-cyclopentapyrazole-3-carboxylic acid amide (739 mg, 3.07 mmol, 18% yield) isolated as a white solid followed by 1-benzyl-1,4,5,6-tetrahydro-cyclopentapyrazole-3-carboxylic acid amide (3.24 g, 13.4 mmol, 79% yield) isolated as a white solid.

Workup

  1. filtrationfiltered
  2. washThe filtrate was washed with H2O (100 mL)
  3. extractionthe aqueous phase was back-extracted with EtOAc (75 mL) and CH2Cl2 (75 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by silica gel chromatography (50% EtOAc in hexanes gradient to 95% EtOAc in hexanes)

Sources & evidence

ORD record
ord-614abc68c85742719d31fd47f54b3dc9
Source dataset
uspto-grants-2014_01
Patent number
US08637555B2

Reaction notes

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