Sodium Carbonate → 3-(5,6-dihydro-2H-pyran-3-yl)-2-fluoropyridine

HRID 473653Notes

Reaction equation

HRID 473653 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)S(O[C:13]1[CH2:14][O:15][CH2:16][CH2:17][CH:18]=1)(=O)=O.[F:21][C:22]1[C:27](B(O)O)=[CH:26][CH:25]=[CH:24][N:23]=1>COCCOC.CCOC(C)=O.O.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>[O:15]1[CH2:16][CH2:17][CH:18]=[C:13]([C:27]2[C:22]([F:21])=[N:23][CH:24]=[CH:25][CH:26]=2)[CH2:14]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 593272465,6-dihydro-2H-pyran-3-yl trifluoromethanesulfonate

Product 1

HCID 593270283-(5,6-dihydro-2H-pyran-3-yl)-2-fluoropyridine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Sodium carbonate (29.0 mL, 58.0 mmol, 2.0 M in water) was added via syringe to a stirred mixture of 5,6-dihydro-2H-pyran-3-yl trifluoromethanesulfonate (4.49 g, 19.3 mmol), 2-fluoropyridine-3-boronic acid (2.72 g, 19.3 mmol), and tetrakis(triphenylphosphine)palladium (1.12 g, 0.97 mmol) in DME (82 mL) under an argon atmosphere. The reaction mixture was stirred at 80° C. for 17 h. The reaction mixture was then cooled to room temperature before being diluted with EtOAc and water. The organic layer was separated, washed with sat. aqueous sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel chromatography to give 3-(5,6-dihydro-2H-pyran-3-yl)-2-fluoropyridine. MS (ESI, pos. ion) m/z: 180.1 (M+1).

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed with sat. aqueous sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-c3210abbf16f4b85b926a75da9c722b9
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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