Phosphorus oxychloride → 1-Chloro-3-(4-fluorophenyl)-6-methoxyisoquinoline

HRID 1852099Notes

Reaction equation

HRID 1852099 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10](O)[C:11]3[C:16]([CH:17]=2)=[CH:15][C:14]([O:18][CH3:19])=[CH:13][CH:12]=3)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:23]>>[Cl:23][C:10]1[C:11]2[C:16](=[CH:15][C:14]([O:18][CH3:19])=[CH:13][CH:12]=2)[CH:17]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487731HCID 178487731, compound

Product 1

HCID 866831881-Chloro-3-(4-fluorophenyl)-6-methoxyisoquinolineYield 91%

Procedure

A solution of 3-(4-fluorophenyl)-6-methoxyisoquinolin-1-ol (350 mg, 1.300 mmol) in POCl3 (1.82 ml, 19.50 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. The crude material was purified by silica gel chromatography using 50% DCM in Hexanes as eluent. The product fractions were collected and the solvent removed under vacuum to give 1-chloro-3-(4-fluorophenyl)-6-methoxyisoquinoline (340 mg, 91% yield). MS: MS m/z 288.1 (M++1).

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
  7. customThe crude material was purified by silica gel chromatography
  8. customThe product fractions were collected
  9. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-5e28e66a1ebc486a85b98ca6c29af0e3
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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