Phosphorus trichloride → 6-Amino-4-chloro-2-methylnicotinonitrile

HRID 928411Notes

Reaction equation

HRID 928411 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9]#[N:10])=[C:4]([O-])[CH:3]=1.[Na+].P(Cl)(Cl)[Cl:14].O=P(Cl)(Cl)Cl>[OH-].[Na+]>[NH2:1][C:2]1[CH:3]=[C:4]([Cl:14])[C:5]([C:9]#[N:10])=[C:6]([CH3:8])[N:7]=1

Participants

5

Reactant 3

HCID 24387Phosphorus trichlorideHCID 24813Phosphorus oxychlorideHCID 58081220Sodium 6-amino-3-cyano-2-methylpyridin-4-olate

Product 1

HCID 672084926-Amino-4-chloro-2-methylnicotinonitrile

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

A suspension of sodium 6-amino-3-cyano-2-methylpyridin-4-olate (690 mg, 4.03 mmol, prepared in analogy to WO2001062233A2 and isolated as sodium salt) in PCl3 (3.50 ml, 40.3 mmol) and POCl3 (0.94 ml, 10.1 mmol) was heated to reflux for 12 h. After cooling to room temperature, the reaction mixture was carefully given onto 2N NaOH (200 ml) and 50 g ice. The mixture was extracted with DCM (7×50 ml), and the combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude product was used without additional purification. LCMS RtM=1.45 min, [M+H]+=168.1.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 12 h
  3. extractionThe mixture was extracted with DCM (7×50 ml)
  4. dry with materialthe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was used without additional purification
  8. customLCMS RtM=1.45 min, [M+H]+=168.1

Sources & evidence

ORD record
ord-87ecdb351084450eac2bdc40a97eff85
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

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