Sodium Carbonate → 3-(3,6-dihydro-2H-pyran-4-yl)-2-fluoropyridine

HRID 410209Notes

Reaction equation

HRID 410209 reaction equation
Br[C:2]1[C:3]([F:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[O:9]1[CH2:14][CH:13]=[C:12](B2OC(C)(C)C(C)(C)O2)[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[O:9]1[CH2:10][CH:11]=[C:12]([C:2]2[C:3]([F:8])=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:13][CH2:14]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27627783-Bromo-2-fluoropyridineHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol ester

Product 1

HCID 593267823-(3,6-dihydro-2H-pyran-4-yl)-2-fluoropyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a round bottomed flask was added 3-bromo-2-fluoropyridine (5.2201 g, 29.7 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7.79 g, 37.1 mmol), trans-dichlorobis(triphenylphosphine) palladium (II) (1.666 g, 2.373 mmol), and sodium carbonate (15.72 g, 148 mmol) in DME (47.5 mL) and Water (11.86 mL) to stir at 80° C. overnight. Reaction was allowed to cool to room temperature. The reaction mixture was diluted with water and extracted with DCM. The organic extract was washed with water, brine, dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (40M), eluting with a gradient of 10% to 100% EtOAc in hexane, to provide 3-(3,6-dihydro-2H-pyran-4-yl)-2-fluoropyridine. MS (ESI, pos. ion) m/z: 180.1 (M+1).

Workup

  1. customReaction
  2. temperatureto cool to room temperature
  3. extractionextracted with DCM
  4. extractionThe organic extract
  5. washwas washed with water, brine
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed through a Biotage pre-packed silica gel column (40M)
  10. washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-ef0870f031764aa282b45a543c4fc82b
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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