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

HRID 1524908Notes

Reaction equation

HRID 1524908 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

6

Reactant 3

HCID 138875Benzoic acid, 2-bromo-5-fluoro-, methyl esterHCID 516892Sodium BicarbonateHCID 112519791H-Pyrazole-5-boronic acid

Product 1

HCID 67086678methyl 5-fluoro-2-(1H-pyrazol-5-yl)benzoateYield 44.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
23 °C

Procedure

Methyl 2-bromo-5-fluorobenzoate (1.0 g, 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 acetate/hexanes, 0-30%) afforded 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. washsolid rinsed with EtOAc
  9. customThe organic layers were separated
  10. customdried
  11. concentrationconcentrated
  12. customPurification via FCC (ethyl acetate/hexanes, 0-30%)

Sources & evidence

ORD record
ord-9d9f109fa60c4db99e0055b63dd6f80b
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

Loading…