Phosphorus oxychloride → 6-Chloro-3-pyridinecarbonitrile

HRID 128813Notes

Reaction equation

HRID 128813 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([NH2:10])=O)=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O>C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]#[N:10])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 804566-Chloronicotinamide

Product 1

HCID 51520946-Chloro-3-pyridinecarbonitrileYield 83.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of 6-chloropyridine-3-carboxamide (14 g), phosphorous oxychloride (35 ml) and chloroform (120 ml) is refluxed for 2 hr, cooled, and concentrated. The residue is stirred with water and the resulting precipitate is collected and recrystallized from ethanol to provide 10.3 g (83 %) of 6-chloropyridine-3-carbonitrile. This nitrile (2.77 g) is added to a solution of sodium octanolate (prepared from 1-octanol (2.78 g) and sodium hydride (0.88g of 60% dispersion) in DMF (20 ml)). After 30 min at room temperature, the mixture is poured into water, and the product extracted with ether. The extracts are concentrated and chromatographed with 2:3 hexane-dichloromethane, to provide 6-(octyloxy)pyridine-3-carbonitrile as a colorless oil (3.7 g, 80%). This nitrile is dissolved in toluene (15 ml), cooled to -20°, and diisobutylaluminum hydride (12.5 ml of 1.5M solution in toluene) is added dropwise. After an hour, the mixture is poured into 1.0N hydrochloric acid and the product extracted with ether. The extracts are dried, filtered, and concentrated to leave 6-(octyloxy)pyridine-3-carboxaldehyde (2.36 g) as a yellow oil.

Workup

  1. temperatureis refluxed for 2 hr
  2. temperaturecooled
  3. concentrationconcentrated
  4. customthe resulting precipitate is collected
  5. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-743c441b308f403b9574329834a14871
Source dataset
uspto-grants-1995_11
Patent number
US05464865

Reaction notes

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