Benzoic acid, 2-bromo-5-fluoro-, methyl ester → methyl 5-fluoro-2-(1H-pyrazol-5-yl)benzoate

HRID 1193108Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[NH:13]1[C:17](B(O)O)=[CH:16][CH:15]=[N:14]1.C([O-])(O)=O.[Na+]>COCCOC.O>[F:12][C:9]1[CH:10]=[CH:11][C:2]([C:15]2[NH:14][N:13]=[CH:17][CH:16]=2)=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

Conditions

Temperature: 23 °C

Procedure

Methyl 2-bromo-5-fluorobenzoate (1.0 gram, 4.2 mmol) and (1H-pyrazol-5-yl)boronic acid (485 mg, 4.6 mmol) were combined and dissolved in degassed DME (15 ml) then treated with NaHCO3 (706 mg, 8.4 mmol) in water and the reaction purged with bubbling N2 for 5 minutes. The reaction was treated with Pd(PPh3)4 (243 mg (0.2 mmol) and then purged with bubbling for 5 minutes in a sealed vessel and then heated to reflux for 2 h. The reaction mixture was cooled to 23° C., filtered, and solid rinsed with EtOAc. The organic layers were separated, dried and concentrated. Purification via FCC (ethyl acatate/hexanes, 0-30%) afforded methyl 5-fluoro-2-(1H-pyrazol-5-yl)benzoate (415 mg, 44%).

Workup

customthe reaction purged with bubbling N2 for 5 minutes
additionThe reaction was treated with Pd(PPh3)4 (243 mg (0.2 mmol)
custompurged
customwith bubbling for 5 minutes in a sealed vessel
temperatureheated
temperatureto reflux for 2 h
filtrationfiltered
washsolid rinsed with EtOAc
customThe organic layers were separated
customdried
concentrationconcentrated
customPurification via FCC (ethyl acatate/hexanes, 0-30%)

Sources & evidence

ORD record: ord-eb3c84795bad43ab9ad4443559f91b3e
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680275B2

Reaction notes

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