Sodium Bicarbonate → 3-fluoro-2-(1H-pyrazol-5-yl)benzonitrile
Reaction equation
Br[C:2]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[NH:11]1[C:15](B(O)O)=[CH:14][CH:13]=[N:12]1.C([O-])(O)=O.[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:10][C:9]1[C:2]([C:13]2[NH:12][N:11]=[CH:15][CH:14]=2)=[C:3]([CH:6]=[CH:7][CH:8]=1)[C:4]#[N:5]Participants
7
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 23 °C
Procedure
2-Bromo-3-fluorobenzonitrile (1.0 g, 5.0 mmol) and (1H-pyrazol-5-yl)boronic acid (647 mg, 4.6 mmol) were combined and dissolved in degassed DME (15 mL) then treated with NaHCO3 (1260 mg, 8.4 mmol) in water and the reaction purged with bubbling N2 for 5 minutes. The reaction was treated with Pd(PPh3)4 (288 mg, 0.2 mmol) and then purged with bubbling for 5 minutes in a sealed vessel and then heated to reflux for 2 h. Cooled to 23° C. filtered and solid rinsed with EtOAc and the layers separated. The organic layers were combined, dried and concentrated under reduced pressure. Chromatography (0-30% ethyl acatate/hexanes) afforded 3-fluoro-2-(1H-pyrazol-5-yl)benzonitrile (178 mg, 19%).
Workup
- customthe reaction purged with bubbling N2 for 5 minutes
- custompurged
- customwith bubbling for 5 minutes in a sealed vessel
- temperatureheated
- temperatureto reflux for 2 h
- filtrationfiltered
- washsolid rinsed with EtOAc
- customthe layers separated
- customdried
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-326028f97fa34fb0add83e55efb1b126
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08680275B2
Reaction notes
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