Phosphorus oxychloride → 4-Chloro-7-methylquinoline-2-carbonitrile

HRID 922749Notes

Reaction equation

HRID 922749 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]#[N+:13][O-])=[N:9]2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:17]>C(Cl)(Cl)Cl>[Cl:17][C:6]1[C:5]2[C:10](=[CH:11][C:2]([CH3:1])=[CH:3][CH:4]=2)[N:9]=[C:8]([C:12]#[N:13])[CH:7]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 895438927-methylquinoline-2-carbonitrile N-oxide

Product 1

HCID 597749194-Chloro-7-methylquinoline-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
70 °C

Procedure

7-Methylquinoline-2-carbonitrile N-oxide (1-4, 5.3 g, 28.8 mmol, 1.0 equiv.) was dissolved in CHCl3 (80 ml, 0.36 M), and POCl3 was added (16.09 ml, 173 mmol, 6.0 equiv.). The mixture was heated to 70° C. overnight, quenched onto crushed ice and extracted three times with dichloromethane. The combined organic layers were washed with water followed by saturated aqueous sodium bicarbonate, dried over MgSO4, filtered and the solvent was removed to yield crude yellow solid. Recrystallization from heptane/EtOAc gave 95 g of 4-chloro-7-methylquinoline-2-carbonitrile (1-5). LRMS m/z (M+H)+203.2 found, 203.6 required.

Workup

  1. customquenched
  2. customonto crushed ice
  3. extractionextracted three times with dichloromethane
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent was removed
  8. customto yield crude yellow solid
  9. customRecrystallization from heptane/EtOAc

Sources & evidence

ORD record
ord-df894fe17f194b8fba3d14d621e8d34e
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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