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

HRID 1880076Notes

Reaction equation

HRID 1880076 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-f5b3918d28a74f45b7afb59b008482f4
Source dataset
uspto-grants-2012_11
Patent number
US08318718B2

Reaction notes

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