Phosphorus oxychloride → 1-Chloro-6-ethoxyisoquinoline

HRID 1821601Notes

Reaction equation

HRID 1821601 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](=O)[NH:9][CH:8]=[CH:7]2)[CH3:2].O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:10]1[C:11]2[C:6](=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[CH:13][CH:12]=2)[CH:7]=[CH:8][N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 578930896-Ethoxyisoquinolin-1(2H)-one

Product 1

HCID 578931101-Chloro-6-ethoxyisoquinolineYield 88%

Conditions

Temperature
110 °C

Procedure

A suspension of 6-Ethoxy-2H-isoquinolin-1-one (896 mg, 4.74 mmol) in POCl3 (4 mL) was heated at 110° C. for 3 h (clear solution obtained upon heating). After 3 h, the reaction mixture was concentrated under reduced pressure. The residue was poured into iced water (10 mL), pH was then adjusted to 10 with 3N NaOH and extracted with CHCl3 (3×25 mL). The combined CHCl3 layers were washed with brine and dried (MgSO4). The organic layer was then filtered and concentrated to give 1-chloro-6-ethoxy-isoquinoline (866 mg, 4.18 mmol, 88% yield, >90% pure) as tan solid. MS m/z 208 (M++H).

Workup

  1. custom(clear solution obtained upon heating)
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. additionThe residue was poured into iced water (10 mL), pH
  4. extractionextracted with CHCl3 (3×25 mL)
  5. washThe combined CHCl3 layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationThe organic layer was then filtered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-05aae665e95a47098335e898e6c56931
Source dataset
uspto-grants-2009_10
Patent number
US07608592B2

Reaction notes

Loading…