Carbon Dioxide → 1-tert-Butyl-1H-pyrazole-4-carboxylic acid

HRID 1930361Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][N:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[CH:6]=1.[Li]CCCC.[C:16](=[O:18])=[O:17]>C1COCC1>[C:7]([N:5]1[CH:6]=[C:2]([C:16]([OH:18])=[O:17])[CH:3]=[N:4]1)([CH3:10])([CH3:9])[CH3:8]

Participants

Conditions

Temperature: -78 °C

Procedure

To a −78° C. solution of 4-bromo-1-t-butyl-1H-pyrazole (15 g, 74.3 mmol) in anhydrous THF (100 mL) was added n-BuLi (2.5 M in hexane, 53 mL, 132 mmol) under N2, and the resulting mixture was stirred at −78° C. for 30 min. Excess dry ice was added at −78° C., and the mixture was warmed slowly to RT and stirred overnight. The reaction was concentrated in vacuo, water was added and the pH was adjusted to pH 3 by the addition of 2N aq HCl. The aqueous solution was extracted with EtOAc. The extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was recrystallized (EtOAc-pet. ether) to give 1-t-butyl-1H-pyrazole-4-carboxylic acid (8.0 g, 67% yield). 1H NMR (300 MHz, CDCl3): δ 8.10 (s, 1 H), 8.03 (s, 1 H), 1.64 (s, 9 H); MS (ESI) m/z: 168.9 [M+H]+.

Workup

temperaturethe mixture was warmed slowly to RT
stirringstirred overnight
concentrationThe reaction was concentrated in vacuo, water
additionwas added
additionthe pH was adjusted to pH 3 by the addition of 2N aq HCl
extractionThe aqueous solution was extracted with EtOAc
washThe extracts were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe residue was recrystallized (EtOAc-pet. ether)

Sources & evidence

ORD record: ord-2e5d6ab72fb946d08de5af6548adf38c
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188113B2

Reaction notes

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