Phosphorus oxychloride → HCID 86683185, compound

HRID 1852091Notes

Reaction equation

HRID 1852091 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH:20]([CH3:22])[CH3:21])=[CH:15][CH:14]=3)[N:8]=[C:9]2O)=[CH:4][C:3]=1[O:23][CH3:24].O=P(Cl)(Cl)[Cl:27]>>[Cl:27][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:23][CH3:24])=[C:2]([F:1])[CH:11]=2)[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH:20]([CH3:22])[CH3:21])=[CH:15][CH:14]=2)[N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178486572HCID 178486572, compound

Product 1

HCID 86683185HCID 86683185, compoundYield 95%

Procedure

A solution of 7-fluoro-3-(4-isopropoxyphenyl)-6-methoxyisoquinolin-1-ol (1.8 g, 5.50 mmol) in POCl3 (7.69 ml, 82 mmol) was refluxed 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. The product fractions were collected and the solvent removed under vacuum to give 1-chloro-7-fluoro-3-(4-isopropoxyphenyl)-6-methoxyisoquinoline (1.8 g, 95% yield). MS: MS m/z 346.1 (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-08ee3a97225b414c90d3cdab829aae9c
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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