Pyridine → 4,6-Dichloropyridine-3-carbonitrile

HRID 1483722Notes

Reaction equation

HRID 1483722 reaction equation
N1C=CC=CC=1.[Cl:7][C:8]1[C:13]([C:14]([NH2:16])=O)=[CH:12][N:11]=[C:10]([Cl:17])[CH:9]=1.O=P(Cl)(Cl)Cl.[OH-].[Na+]>C(#N)C>[Cl:7][C:8]1[C:13]([C:14]#[N:16])=[CH:12][N:11]=[C:10]([Cl:17])[CH:9]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 6000444,6-Dichloronicotinamide

Product 1

HCID 455880804,6-Dichloropyridine-3-carbonitrileYield 88.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

Pyridine (20.3 mL, 250 mmol) was added to a suspension of 4,6-dichloro-nicotinamide (8.00 g, 41.9 mmol) in acetonitrile (180 mL) at room temperature POCl3 (11.7 mL, 126 mmol) was added over 3 minutes at room temperature. The reaction mixture was heated at 60° C. with for 1.5 hours. The reaction solution was cooled to room temperature and poured into aqueous NaOH (0.8M, 600 mL) followed by extraction with EtOAc (6×400 mL). The organic extracts were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash column chromatography (30% ethyl acetate/hexanes) to give the title compound as a light orange solid (6.41 g, 88%)

Workup

  1. additionwas added over 3 minutes at room temperature
  2. temperatureThe reaction solution was cooled to room temperature
  3. extractionfollowed by extraction with EtOAc (6×400 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel flash column chromatography (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-705e4957f22e4124b8a41975c5beae86
Source dataset
uspto-grants-2016_08
Patent number
US09416146B2

Reaction notes

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