Sodium Carbonate → 3-(3,6-Dihydro-2H-pyran-4-YL)-2,5-difluoro-pyridine

HRID 1846785Notes

Reaction equation

HRID 1846785 reaction equation
Br[C:2]1[C:3]([F:9])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].CC1(C)C(C)(C)OB([C:24]2[CH2:25][CH2:26][O:27][CH2:28][CH:29]=2)O1>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:27]1[CH2:26][CH:25]=[C:24]([C:2]2[C:3]([F:9])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 146006963-Bromo-2,5-difluoropyridine

Product 1

HCID 585486583-(3,6-Dihydro-2H-pyran-4-YL)-2,5-difluoro-pyridineYield 90.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-bromo-2,5-difluoro-pyridine (4.1 g, 20.8 mmol) in dioxane (60 mL) was treated with Na2CO3 (4.4 g, 41.6 mmol) in 20 mL of H2O as a solution, followed by additional of 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (4.8 g 22.9 mmol) and Pd(dppf)Cl2 (761 mg). The resulting mixture was heated at refluxing overnight under N2 atmosphere. TLC showed that most of the staring materials were consumed. The solution was filtered and the filtrate was concentrated to get a residue, which was purified by silica gel chromatography to give the product (3.7 g).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat refluxing overnight under N2 atmosphere
  3. customwere consumed
  4. filtrationThe solution was filtered
  5. concentrationthe filtrate was concentrated
  6. customto get a residue, which
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-f3fab060d57f4e509e24eee64a56e01f
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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