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

HRID 1842517Notes

Reaction equation

HRID 1842517 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[O:7]1[CH2:12][CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH2:9][CH2:8]1.Br[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([F:29])[CH:24]=1.[Cl-].[NH4+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[O:7]1[CH2:12][CH:11]=[C:10]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([F:29])[CH:24]=2)[CH2:9][CH2:8]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 27628514-Bromo-2-fluoropyridineHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol ester

Product 1

HCID 585484534-(3,6-dihydro-2H-pyran-4-yl)-2-fluoropyridineYield 89%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tetrakis(triphenylphosphine)palladium(0) (0.20 g, 0.17 mmol), aqueous sodium carbonate (2N aqueous, 8.52 mL, 17.05 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.43 g, 6.82 mmol), and 4-bromo-2-fluoropyridine (1.0 g, 5.68 mmol) in 1,2-dimethoxyethane (25 mL) was placed under argon atmosphere using 3 evacuation/backfill cycles. The mixture was then heated to 80° C. for 16 h then cooled to RT. Ethyl acetate and saturated aqueous ammonium chloride were added and the layers of the resulting biphasic mixture were separated. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil that was purified by silica gel chromatography to give 4-(3,6-dihydro-2H-pyran-4-yl)-2-fluoropyridine (0.90 g, 5.0 mmol, 89% yield) as a light yellow solid.

Workup

  1. temperaturethen cooled to RT
  2. customthe layers of the resulting biphasic mixture were separated
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give an oil that
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-790dc212df1144088b1cb610fa84feae
Source dataset
uspto-grants-2015_02
Patent number
US08946230B2

Reaction notes

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