Carbon Dioxide → 1-cyclopentyl-1H-pyrazole-4-carboxylic acid
Reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=1.[Li]CCCC.[C:17](=[O:19])=[O:18]>C1COCC1>[CH:7]1([N:5]2[CH:6]=[C:2]([C:17]([OH:19])=[O:18])[CH:3]=[N:4]2)[CH2:11][CH2:10][CH2:9][CH2:8]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 4-bromo-1-cyclopentyl-1H-pyrazole (9.0 g, 42 mmol) in THF (100 mL) at −78° C. under nitrogen was added a solution of n-BuLi in hexanes (2.5 M, 18.5 mL, 46.2 mmol). The resulting mixture was stirred at −78° C. for 30 min. Dry-ice (solid CO2) was added at −78° C. and the reaction mixture was allowed to slowly warn to RT overnight. The solvent was removed under reduced pressure. Water was added, and the mixture was acidified (pH 3) by the addition of aq. HCl. The aqueous layer was extracted with EtOAc, and the extracts were washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was recrystallized (EtOAc-petroleum ether) to provide 1-cyclopentyl-1H-pyrazole-4-carboxylic acid (3.5 g, 47% yield). 1H NMR (400 MHz, DMSO-d6): δ 12.50 (br s, 1 H), 8.31 (s, 1 H), 7.85 (s, 1 H), 4.78 (m, 1 H), 2.16-1.68 (m, 8 H); MS (ESI) m/z: 181.0 [M+H]+.
Workup
- waitto slowly warn to RT overnight
- customThe solvent was removed under reduced pressure
- additionWater was added
- additionby the addition of aq. HCl
- extractionThe aqueous layer was extracted with EtOAc
- washthe extracts were washed with brine
- dry with materialdried over MgSO4
- concentrationconcentrated in vacuo
- customThe residue was recrystallized (EtOAc-petroleum ether)
Sources & evidence
- ORD record
- ord-4aa6626c1f3443eb893075463808c4b5
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08143293B2
Reaction notes
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