Phosphorus oxychloride → HCID 178426119, compound

HRID 1501261Notes

Reaction equation

HRID 1501261 reaction equation
[OH:1][C:2]1[N:9]=[C:8]([CH3:10])[CH:7]=[C:6](O)[C:3]=1[C:4]#[N:5].P(Cl)(Cl)([Cl:14])=O>C(#N)C.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[Cl:14][C:6]1[C:3]([C:4]#[N:5])=[C:2]([OH:1])[N:9]=[C:8]([CH3:10])[CH:7]=1

Participants

5

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178429083HCID 178429083, compound

Product 1

HCID 178426119HCID 178426119, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2,4-dihydroxy-6-methylnicotinonitrile (1.5 g, 10 mmol) in acetonitrile (50 mL) were added benzyltriethylammonium chloride (9.1 g, 40 mmol) and phosphoryl chloride (6.13 g, 40 mmol). The reaction mixture was heated to 40° C. for 4 hours. The solvent was removed by rotary evaporation, to the residue was added dichloromethane (100 mL) and water (50 mL), the organic phase was separated, and washed with brine (50 mL) once, dried by anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give crude product which was purified by silica gel column chromatography with dichloromethane/methanol=10:1 to afford 4-chloro-2-hydroxy-6-methylnicotinonitrile (800 mg, 24% yield) as a brown solid.

Workup

  1. customThe solvent was removed by rotary evaporation, to the residue
  2. additionwas added dichloromethane (100 mL) and water (50 mL)
  3. customthe organic phase was separated
  4. washwashed with brine (50 mL) once
  5. dry with materialdried by anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give crude product which
  9. customwas purified by silica gel column chromatography with dichloromethane/methanol=10:1

Sources & evidence

ORD record
ord-87594dccef8f468d9cec017fe0ab0e14
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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