Potassium Phosphate, Tribasic → 3-Cyclopropyl-2-fluoropyridine

HRID 410168

Reaction equation

HRID 410168 reaction equation
Br[C:2]1[C:3]([F:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH:9]1(B(O)O)[CH2:11][CH2:10]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH:9]1([C:2]2[C:3]([F:8])=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:11][CH2:10]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 27627783-Bromo-2-fluoropyridine

Product 1

HCID 593270243-Cyclopropyl-2-fluoropyridine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-bromo-2-fluoropyridine (1.56 g, 8.86 mmol), cyclopropylboronic acid (990 mg, 11.5 mmol), potassium phosphate (6.59 g, 31.0 mmol) and tricyclohexylphosphine (249 mg, 0.89 mmol) in a mixed solvent of toluene (40 mL) and water (2 mL) under a nitrogen atmosphere was added palladium(ii) acetate (99.5 mg, 0.443 mmol). The reaction mixture was heated at 100° C. for 3 h. The mixture was allowed to cool to RT, filtered through a pad of Celite™ and washed with EtOAc. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (120 g), eluting with a gradient of 0% to 10% EtOAc in hexane, to provide 3-cyclopropyl-2-fluoropyridine as light-yellow oil.

Workup

  1. temperatureto cool to RT
  2. filtrationfiltered through a pad of Celite™
  3. washwashed with EtOAc
  4. customThe crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (120 g)
  5. washeluting with a gradient of 0% to 10% EtOAc in hexane

Sources & evidence

ORD record
ord-80401d31c096477a8c2f1a722d19780a
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Linked notes

Loading…