Phosphorus oxychloride → 2-chloro-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonitrile

HRID 1771519Notes

Reaction equation

HRID 1771519 reaction equation
O=[C:2]1[NH:7][C:6]2[CH2:8][CH2:9][O:10][CH2:11][C:5]=2[CH:4]=[C:3]1[C:12]#[N:13].C(=O)([O-])O.[Na+].P(Cl)(Cl)([Cl:21])=O>>[Cl:21][C:2]1[N:7]=[C:6]2[CH2:8][CH2:9][O:10][CH2:11][C:5]2=[CH:4][C:3]=1[C:12]#[N:13]

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 509903192-hydroxy-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonitrile

Product 1

HCID 616589142-chloro-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonitrileYield 66%

Procedure

step 2 2-Oxo-1,5,7,8-tetrahydro-2H-pyrano[4,3-b]pyridine-3-carbonitrile (2.50 g, 14.4 mmol) obtained in step 1 was dissolved in phosphoryl chloride (20 mL), and the mixture was stirred with heating under reflux for 4 hr. The mixture was allowed to cool to room temperature, and slowly added to a saturated aqueous sodium hydrogen carbonate solution at 0° C., then the mixture was extracted with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50) to give 2-chloro-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonitrile (1.85 g, 66%) as a white solid.

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 4 hr
  3. extractionthe mixture was extracted with chloroform
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50)

Sources & evidence

ORD record
ord-3dc178b0cbd3483c9c64534e2f2e47d3
Source dataset
uspto-grants-2016_02
Patent number
US09249135B2

Reaction notes

Loading…