Phosphorus oxychloride → 1-Chloro-7-fluoro-5-methoxyisoquinoline

HRID 1852114Notes

Reaction equation

HRID 1852114 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2O)=[C:4]([O:13][CH3:14])[CH:3]=1.O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:9]1[C:10]2[C:5](=[C:4]([O:13][CH3:14])[CH:3]=[C:2]([F:1])[CH:11]=2)[CH:6]=[CH:7][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178492918HCID 178492918, compound

Product 1

HCID 717427031-Chloro-7-fluoro-5-methoxyisoquinolineYield 95.1%

Procedure

A solution of 7-fluoro-5-methoxyisoquinolin-1-ol (383 mg, 1.983 mmol) in POCl3 (2772 μl, 29.7 mmol) was refluxed (90° C.) for 4 h. The reaction mixture was concentrated. The residue was dissolved in DCM and the pH was adjusted to 7 with 4N NaOH. The organic phase was collected and dried over sodium sulfate, filtered, then concentrated under vacuum to give 1-chloro-7-fluoro-5-methoxyisoquinoline (399 mg, 95% yield).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was dissolved in DCM
  3. customThe organic phase was collected
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4ee6c1ae65fa4e989a96ef2946588207
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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