Cesium carbonate → 3-Fluoro-4-(pyrimidin-5-yl)picolinonitrile

HRID 871158Notes

Reaction equation

HRID 871158 reaction equation
[F:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[CH:6][C:7]=1I.[N:11]1[CH:16]=[C:15](B(O)O)[CH:14]=[N:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C(Cl)Cl>[F:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[CH:6][C:7]=1[C:15]1[CH:16]=[N:11][CH:12]=[N:13][CH:14]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 210758673-Fluoro-4-iodopyridine-2-carbonitrile

Product 1

HCID 867304123-Fluoro-4-(pyrimidin-5-yl)picolinonitrileYield 44.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A vial containing a mixture of 3-fluoro-4-iodopicolinonitrile (3.0 g, 12.10 mmol), pyrimidin-5-ylboronic acid (5.23 g, 42.2 mmol), and cesium carbonate (8.28 g, 25.4 mmol) in dioxane (Ratio: 2.0, Volume: 24.44 ml) and water (Ratio: 1.000, Volume: 12.22 ml) was degassed with N2 for 5 min, then PdCl2(dppf)-CH2Cl2Adduct (0.524 g, 0.641 mmol) was added. The solution was heated at 85° C. for 21 hr, and then allowed to cool to room temperature. The reaction was quenched with water. The reaction mixture was diluted with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried over Na2SO4, filtered, and concentrated to afford a brown residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (120 g column, 85 mL/min, 50-90% EtOAc in hexanes over 25 min, tr=10 min) gave the title compound (1.089 g, 5.39 mmol, 44.5% yield) as an orange solid.

Workup

  1. additionA vial containing
  2. customwas degassed with N2 for 5 min
  3. temperatureto cool to room temperature
  4. customThe reaction was quenched with water
  5. additionThe reaction mixture was diluted with EtOAc
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with EtOAc (3×)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a brown residue
  12. customto be chromatographed
  13. customPurification of the crude material by silica gel chromatography
  14. customan ISCO machine (120 g column, 85 mL/min, 50-90% EtOAc in hexanes over 25 min, tr=10 min)

Sources & evidence

ORD record
ord-d405b91a759941ce9e3c71f233eb39c8
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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