Phosphorus oxychloride → 4-Chloro-7-methoxy-2-phenylquinoline

HRID 553437Notes

Reaction equation

HRID 553437 reaction equation
[C:1]1([C:7]2[CH:16]=[C:15](O)[C:14]3[C:9](=[CH:10][C:11]([O:18][CH3:19])=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)([Cl:22])=O>>[C:1]1([C:7]2[CH:16]=[C:15]([Cl:22])[C:14]3[C:9](=[CH:10][C:11]([O:18][CH3:19])=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487676HCID 178487676, compound

Product 1

HCID 107544774-Chloro-7-methoxy-2-phenylquinolineYield 91%

Procedure

2-phenyl-4-hydroxy-7-methoxy-quinoline (2.73 g, 10.9 mmol., 1 eq) was suspended in neat phosphorus oxychloride (30 mL). The reaction mixture was heated under reflux. After 2 h, LCMS analysis showed full consumption of the starting material. The reaction mixture was left to cool to ambient temperature and the solvent removed under vacuum. The residue was partitioned between ethyl acetate (100 mL) and 2M aqueous sodium hydroxide solution (80 mL). The mixture was stirred at ambient temperature for a further 10 min, and then the two layers were separated. The organic phase was washed with water (2×50 mL) and saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered and the solvent removed under vacuum. The obtained beige solid was further dried under high vacuum for 2 hours to give 2.66 g (91%) of the title compound. 1H NMR (250 MHz, DMSO-d6) δ ppm 8.25-8.35 (m, 2H), 8.21 (s, 1 H), 8.09 (d, J=9.14 Hz, 1 H), 7.47-7.61 (m, 4H), 7.38 (dd, J=2.55, 9.18 Hz, 1 H), 3.97 (s, 3 H). LC-MS: purity 100% (UV), tR 2.58 min, m/z [M+1]+ 270.00.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux
  3. customconsumption of the starting material
  4. waitThe reaction mixture was left
  5. customthe solvent removed under vacuum
  6. customThe residue was partitioned between ethyl acetate (100 mL) and 2M aqueous sodium hydroxide solution (80 mL)
  7. customthe two layers were separated
  8. washThe organic phase was washed with water (2×50 mL) and saturated aqueous sodium chloride solution (50 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customthe solvent removed under vacuum
  12. customThe obtained beige solid was further dried under high vacuum for 2 hours

Sources & evidence

ORD record
ord-5a31fcf2af4c4764b6d72009e8ee3319
Source dataset
uspto-grants-2011_11
Patent number
US08048862B2

Reaction notes

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