Hydrochloric Acid → 3-tert-butyl-1H-pyrazole-5-carboxylic acid

HRID 1063800Notes

Reaction equation

C([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[NH:8][N:7]=1)=[O:5])C.[OH-].[Na+].Cl>O1CCOCC1>[C:11]([C:9]1[NH:8][N:7]=[C:6]([C:4]([OH:5])=[O:3])[CH:10]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

Conditions

Temperature: 60 °C

Procedure

5-tert-Butyl-1H-pyrazol-3-carboxylic acid ethyl ester (20 g, 100 mmol) and 1M NaOH solution (250 ml, 250 mmol) were dissolved in 1,4-dioxan (300 ml), the reaction was heated to 60° C. under nitrogen and stirred for 2.5 hours. The reaction was then cooled to room temperature and stirred for a further 18 hours. The reaction mixture was adjusted to pH 2 using concentrated hydrochloric acid, extracted with ethyl acetate (4×200 ml) and the combined organic extracts washed with brine (100 ml). The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure to give 5-tert-butyl-1H-pyrazol-3-carboxylic acid (14.7 g) as a pale yellow solid. 1H NMR (400 MHz, DMSO-D6): δ=12.80-12.88 (2H, brs), 6.41 (1H, s), 1.11 (9H, s) ppm. LRMS (electrospray): m/z [M+H]+ 169, [M+Na]+ 191, [M−H]+ 167.

Workup

temperatureThe reaction was then cooled to room temperature
stirringstirred for a further 18 hours
extractionextracted with ethyl acetate (4×200 ml)
washthe combined organic extracts washed with brine (100 ml)
dry with materialThe organic phase was dried over MgSO4
customthe solvent was removed under reduced pressure

Sources & evidence

ORD record: ord-45cbda5dc488459a82113b171d051644
Source dataset: uspto-grants-2005_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06967204B2

Reaction notes

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