Hydrochloric Acid → 1-(4-(1,3,4-oxadiazol-2-yl)phenyl)-3-tert-butyl-1H-pyrazole-5-carboxylic acid

HRID 1930431Notes

Reaction equation

[O:1]1[CH:5]=[N:4][N:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([C:17]([O:19]CC)=[O:18])=[CH:15][C:14]([C:22]([CH3:25])([CH3:24])[CH3:23])=[N:13]2)=[CH:8][CH:7]=1.C1COCC1.[OH-].[Li+].Cl>O.CO>[O:1]1[CH:5]=[N:4][N:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([C:17]([OH:19])=[O:18])=[CH:15][C:14]([C:22]([CH3:25])([CH3:24])[CH3:23])=[N:13]2)=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of ethyl 1-(4-(1,3,4-oxadiazol-2-yl)phenyl)-3-tert-butyl-1H-pyrazole-5-carboxylate (440 mg, 1.29 mmol) in a mixture comprised of THF (3 mL), methanol (1 mL) and water (1 mL) was cooled to 0° C. and treated with lithium hydroxide (62 mg, 2.59 mmol). The reaction mixture was stirred 3 h at 0° C. and was then allowed to warm to RT over 4 h. Water (15 mL) was added and the mixture was extracted with ether (2×10 mL). The aqueous portion was acidified by addition of 1 M aq HCl (2.5 mL, 2.5 mmol) and was extracted with EtOAc (3×20 mL). The organics were dried (Na2SO4) and concentrated in vacuo to provide 1-(4-(1,3,4-oxadiazol-2-yl)phenyl)-3-tert-butyl-1H-pyrazole-5-carboxylic acid (355 mg, 88% yield). 1H NMR (400 MHz, DMSO-d6): δ 13.35 (br s, 1 H), 9.40 (d, J=3.4 Hz, 1 H), 8.11 (m, 2 H), 7.69 (m, 2 H), 7.01 (d, J=3.2 Hz, 1 H), 1.32 (s, 9 H); MS (ESI) m/z: 313.0 (M+H+).

Workup

temperatureto warm to RT over 4 h
extractionthe mixture was extracted with ether (2×10 mL)
extractionwas extracted with EtOAc (3×20 mL)
dry with materialThe organics were dried (Na2SO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-1062c5427487489caab690c6f0d27cdd
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188113B2

Reaction notes

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