Phosphorus oxychloride → 1-Chloro-7-methylisoquinoline

HRID 651589Notes

Reaction equation

HRID 651589 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=O)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:15])=O>>[Cl:15][C:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([CH3:1])[CH:11]=2)[CH:6]=[CH:7][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 156938767-Methylisoquinolin-1(2H)-one

Product 1

HCID 222501861-Chloro-7-methylisoquinoline

Procedure

7-Methyl-2H-isoquinolin-1-one (2.1 g, 13.2 mmol) in phosphorus oxychloride (30 mL) is heated to reflux for 13 hours. The mixture is cooled to room temperature, then concentrated to a smaller volume. The residue is diluted with ice water and the pH is adjusted to ca. 8 by slow addition of 10 N NaOH. The aqueous solution is extracted with methylene chloride (4×20 mL) and the combined organic layers are washed with brine, dried over MgSO4, filtered and concentrated. The resulting dark oil is purified by column chromatography eluting with 25% EtOAc/hexanes to give the product (1.6 g, 9 mmol) as a light yellow solid.

Workup

  1. temperatureto reflux for 13 hours
  2. concentrationconcentrated to a smaller volume
  3. additionThe residue is diluted with ice water
  4. additionby slow addition of 10 N NaOH
  5. extractionThe aqueous solution is extracted with methylene chloride (4×20 mL)
  6. washthe combined organic layers are washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting dark oil is purified by column chromatography
  11. washeluting with 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-e2460e2f03a5488d800acb9e578a2bc0
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

Loading…