Phosphorus oxychloride → HCID 86683191, compound

HRID 1852107Notes

Reaction equation

HRID 1852107 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](O)=[N:7][CH:6]=[C:5]2[O:13][CH3:14].O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:8]1[C:9]2[C:4](=[CH:3][C:2]([F:1])=[CH:11][CH:10]=2)[C:5]([O:13][CH3:14])=[CH:6][N:7]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178493786HCID 178493786, compound

Product 1

HCID 86683191HCID 86683191, compoundYield 69.3%

Procedure

A solution of 6-fluoro-4-methoxyisoquinolin-1-ol (2.9 g, 15.01 mmol) in POCl3 (10 ml, 107 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 as eluent. The product fractions were collected and the solvent removed under vacuum to give 1-chloro-6-fluoro-4-methoxyisoquinoline (2.2 g, 67% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.29 (dd, J=9.2, 5.4 Hz, 1H), 7.84-7.79 (m, 2H), 7.45 (ddd, J=9.3, 8.2, 2.6 Hz, 1H), 4.06 (s, 3H); MS m/z 212.0 (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-85839971fbbd4a3e87f39175e53fdf63
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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