1,2-Dimethoxyethane → methyl 5-fluoro-2-(1H-pyrazol-5-yl)benzoate

HRID 1524937Notes

Reaction equation

HRID 1524937 reaction equation
C[C:2]1[CH:10]=[CH:9][C:5](C([O-])=O)=[C:4]([F:11])[C:3]=1Br.[NH:13]1[C:17](B(O)O)=[CH:16][CH:15]=[N:14]1.[C:21]([O-:24])(O)=[O:22].[Na+].[CH3:26]OCCOC>O>[F:11][C:4]1[CH:3]=[CH:2][C:10]([C:17]2[NH:13][N:14]=[CH:15][CH:16]=2)=[C:9]([CH:5]=1)[C:21]([O:24][CH3:26])=[O:22]

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 516892Sodium BicarbonateHCID 112519791H-Pyrazole-5-boronic acidHCID 53430578Methyl-2-fluoro-bromobenzoate

Product 1

HCID 67086678methyl 5-fluoro-2-(1H-pyrazol-5-yl)benzoateYield 44%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
23 °C

Procedure

Methyl-2-fluoro-bromobenzoate (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 the solid was rinsed with EtOAc and the layers separated. The organic layers were combined, dried and concentrated. Chromatography (ethyl acetate/hexanes, 0-30%) gave methyl 5-fluoro-2-(1H-pyrazol-5-yl)benzoate (415 mg, 44%).

Workup

  1. customthe reaction purged with bubbling N2 for 5 minutes
  2. additionThe reaction was treated with Pd(PPh3)4 (243 mg (0.2 mmol)
  3. custompurged
  4. customwith bubbling for 5 minutes in a sealed vessel
  5. temperatureheated
  6. temperatureto reflux for 2 h
  7. filtrationfiltered
  8. washthe solid was rinsed with EtOAc
  9. customthe layers separated
  10. customdried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-05259dbefdcc4a69933dfd3c06934413
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

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