Phosphorus oxychloride → 4-Chloro-3-nitroquinoline

HRID 520270Notes

Reaction equation

HRID 520270 reaction equation
[C@@H]1(N2C3N=CN=C(N)C=3N=C2)O[C@H](CO)[C@@H](O)[C@H]1O.N1C(=O)C2NC=NC=2NC1=O.[N+:31]([C:34]1[CH:35]=[N:36][C:37]2[C:42]([C:43]=1O)=[CH:41][CH:40]=[CH:39][CH:38]=2)([O-:33])=[O:32].P(Cl)(Cl)([Cl:47])=O>>[N+:31]([C:34]1[CH:35]=[N:36][C:37]2[C:42]([C:43]=1[Cl:47])=[CH:41][CH:40]=[CH:39][CH:38]=2)([O-:33])=[O:32]

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 69100026HCID 69100026, compoundHCID 178526762HCID 178526762, compound

Product 1

HCID 112758084-Chloro-3-nitroquinoline

Procedure

Compound 6 was prepared as described elsewhere [Van Galen, P. J. M. et. al. 1-H-imidazo[4,5-c]quinolin-4-amines: Novel Non-Xanthine Adenosine Antagonists. J. Med. Chem. 1991, 34, 1202-1206]. In brief, 3-Nitro-4-hydroxyquinoline 5 (5.7 g, 30 mmol) was added to phosphorus oxychloride (70.0 g, 41.2 ml, 450 mmol) with stirring. The mixture was refluxed for 30 minutes. After cooling the solvent was poured over crushed ice while stirring. After 1 hour the solid that was formed was filtered off, washed with cold water and dissolved in ethyl acetate. The solution was extracted with ice-cold NaOH (1 M) till pH=8-9 and dried over MgSO4. The solvent was evaporated and the residue was dried. Yield: 5.05 g (81%). Mp.: 118°-119° C. 1H NMR (DMSO-d6): δ 7.94-8.11 (m, 2H, Ar); 8.25 (d, 1H, J=8.0 Hz, Ar); 8.47 (d, 1H, J=9.5 Hz, Ar); 9.42 (s, 1H, Ar).

Workup

  1. temperatureThe mixture was refluxed for 30 minutes
  2. temperatureAfter cooling the solvent
  3. additionwas poured
  4. customover crushed ice
  5. stirringwhile stirring
  6. customAfter 1 hour the solid that was formed
  7. filtrationwas filtered off
  8. washwashed with cold water
  9. dissolutiondissolved in ethyl acetate
  10. extractionThe solution was extracted with ice-cold NaOH (1 M) till pH=8-9
  11. dry with materialdried over MgSO4
  12. customThe solvent was evaporated
  13. customthe residue was dried

Sources & evidence

ORD record
ord-eff816a565954695aaef440814884de0
Source dataset
uspto-grants-2016_05
Patent number
US09326978B2

Reaction notes

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