4-Chloropyridine hydrochloride → 2-(2-Methylpyrimidin-5-yl)-2-(pyridin-4-yl)acetonitrile

HRID 512175Notes

Reaction equation

HRID 512175 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][N:3]=1.Cl.Cl[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.CC([O-])(C)C.[K+]>O1CCOCC1>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[C:9]#[N:10])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 818524-Chloropyridine hydrochlorideHCID 23665647Potassium tert-butoxideHCID 847623642-(2-Methylpyrimidin-5-yl)acetonitrile

Product 1

HCID 867162022-(2-Methylpyrimidin-5-yl)-2-(pyridin-4-yl)acetonitrileYield 44.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-(2-methylpyrimidin-5-yl)acetonitrile (1.0 g, 7.51 mmol) and 4-chloropyridine hydrochloride (1.13 g, 7.51) in dioxane (20 mL) in a dried flask was degassed and filled with nitrogen. t-BuOK (18.8 mL, 1M in THF) was added. The mixture was stiffed at 100° C. for 4 h and cooled to room temperature, quenched by cooled sat. aq. NH4Cl (20 mL). The resulting mixture was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (3×10 mL), dried over Na2SO4, concentrated under reduced pressure to give the crude product, which was purified by column chromatography on silica gel (MeOH: EtOAc=1:10) to give 2-(2-methylpyrimidin-5-yl)-2-(pyridin-4-yl)acetonitrile (700 mg, crude).

Workup

  1. additionfilled with nitrogen
  2. customquenched
  3. temperatureby cooled sat. aq. NH4Cl (20 mL)
  4. extractionThe resulting mixture was extracted with EtOAc (3×10 mL)
  5. washThe combined organic layers were washed with brine (3×10 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product, which
  9. customwas purified by column chromatography on silica gel (MeOH: EtOAc=1:10)

Sources & evidence

ORD record
ord-05e62fa75a3b4b0f9ddd4110731017eb
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Reaction notes

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