Phosphorus oxychloride → 1-Chloro-3-methoxyisoquinoline

HRID 1852073Notes

Reaction equation

HRID 1852073 reaction equation
[CH3:1][O:2][C:3]1[NH:4][C:5](=O)[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2.O=P(Cl)(Cl)[Cl:16]>>[Cl:16][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:12]=[C:3]([O:2][CH3:1])[N:4]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 122798821(2H)-Isoquinolinone, 3-methoxy-

Product 1

HCID 222502711-Chloro-3-methoxyisoquinolineYield 44%

Procedure

3-Methoxyisoquinolin-1(2H)-one (2.8 g, 16.0 mmol) in POCl3 (10 mL) was heated to reflux for 3 h then evaporated in vacuo. The residue was poured into iced NaHCO3 solution (50 mL). The product was extracted with EtOAc (2×). The organic layer was washed with brine, dried over MgSO4, filtered, evaporated. The residue was purified by flash chromatography with 20% then 40% of EtOAc/hexane to afford 1.36 g (44%) of the desired product 1-chloro-3-methoxyisoquinoline as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.29-8.16 (d, J=8.3 Hz, 1H), 7.72 (d, J=8.3 Hz, 1H), 7.63 (ddd, J=8.3, 6.8, 1.1 Hz, 1H), 7.47 (ddd, J=8.5, 7.0, 1.1 Hz, 1H), 6.98 (s, 1H), 4.05 (s, 3H). MS: MS m/z 194.0 (M++1).

Workup

  1. temperatureto reflux for 3 h
  2. customthen evaporated in vacuo
  3. additionThe residue was poured into iced NaHCO3 solution (50 mL)
  4. extractionThe product was extracted with EtOAc (2×)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash chromatography with 20%

Sources & evidence

ORD record
ord-45b303e60ba241e694609a9e4937eab2
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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