Hydrochloric Acid → 4-(5-Chloro-2-hydroxyphenyl)pyridine-2-carbonitrile

HRID 1401996Notes

Reaction equation

HRID 1401996 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6](B(O)O)[CH:7]=1.Cl[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([C:19]#[N:20])[CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>O1CCOCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([C:19]#[N:20])[CH:14]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 6933424-Chloro-2-pyridinecarbonitrileHCID 23005362(5-Chloro-2-hydroxyphenyl)boronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 1360636254-(5-Chloro-2-hydroxyphenyl)pyridine-2-carbonitrileYield 8.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

(5-Chloro-2-hydroxyphenyl)boronic acid (2.0 g, 0.012 mol), 4-chloropyridine-2-carbonitrile (1.61 g, 0.012 mol), (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.424 g, 0.00058 mol) and sodium carbonate (3.7 g, 0.035 mol) in 1,4-dioxane (20.0 mL) and deionised water (1.0 mL) were degassed with nitrogen (×3) before heating at 100° C. for 18 hours under nitrogen. The reaction was cooled and hydrochloric acid (2.0 M aqueous solution, 30.0 mL) added. Reaction was filtered, washing with ethyl acetate (50.0 mL). The organic layer was concentrated in vacuo and purified by flash column chromatography on the ISCO™ (40 g SiO2) eluting with ethyl acetate:heptane (gradient 0:1 to 7:3, by volume) to afford the title compound as a yellow solid, 0.23 g, 8.6% yield.

Workup

  1. temperatureThe reaction was cooled
  2. customReaction
  3. filtrationwas filtered
  4. washwashing with ethyl acetate (50.0 mL)
  5. concentrationThe organic layer was concentrated in vacuo
  6. custompurified by flash column chromatography on the ISCO™ (40 g SiO2)
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-cd742c40ab67431480e859cbb4ee5bcc
Source dataset
uspto-grants-2014_12
Patent number
US08907101B2

Reaction notes

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