Pyrazole → 3-Fluoro-2-(1H-pyrazol-1-YL)benzoic acid

HRID 1524942Notes

Reaction equation

[F:1][C:2]1[C:3](I)=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[NH:12]1[CH:16]=[CH:15][CH:14]=[N:13]1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[Cs+].[Cs+]>O.[Cu]I.O1CCOCC1>[F:1][C:2]1[C:3]([N:12]2[CH:16]=[CH:15][CH:14]=[N:13]2)=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6]

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 3-fluoro-2-iodobenzoic acid (1.4 g, 5.26 mmol), 1H-pyrazole (0.72 g, 10.5 mmol), trans-N,N′-dimethyl-cyclohexane-1,2-diamine (0.17 mL, 1.05 mmol), CuI (50.1 mg, 0.26 mmol), dioxane (50 mL) and water (0.028 mL) was added Cs2CO3 (3.43 g, 10.5 mmol). The reaction mixture was heated to 100° C. for 1 h. The reaction mixture was cooled to ambient temperature then diluted with water. The aqueous layer was acidified to pH2 and extracted with EtOAc (30 mL) three times. The organic layers were combined, dried over Na2SO4, filtered and concentrated. Purification (FCC), (DCM to 10% MeOH/1% HOAC/DCM) afforded the title compound as a colorless oil (790 mg, 72%). 1H NMR (400 MHz, CDCl3): 7.85-7.73 (m, 1H), 7.54-7.44 (m, 1H), 7.44-7.34 (m, 1H), 6.55 (s, 1H).

Workup

temperatureThe reaction mixture was cooled to ambient temperature
extractionextracted with EtOAc (30 mL) three times
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customPurification (FCC), (DCM to 10% MeOH/1% HOAC/DCM)

Sources & evidence

ORD record: ord-17a10423db9243e3a066d550f7e6fba0
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079911B2

Reaction notes

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