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

HRID 1852096Notes

Reaction equation

HRID 1852096 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[N:11]=[C:12](O)[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([O:20][CH3:21])=[CH:15][CH:14]=3)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].O=P(Cl)(Cl)[Cl:25]>>[Cl:25][C:12]1[C:13]2[C:18](=[CH:17][C:16]([O:20][CH3:21])=[CH:15][CH:14]=2)[CH:19]=[C:10]([C:4]2[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([F:1])[CH:3]=2)[N:11]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487739HCID 178487739, compound

Product 1

HCID 866831871-Chloro-3-(3-fluoro-4-methoxyphenyl)-6-methoxyisoquinolineYield 95%

Procedure

A solution of 3-(3-fluoro-4-methoxyphenyl)-6-methoxyisoquinolin-1-ol (1.2 g, 4.01 mmol) in POCl3 (5.61 ml, 60.1 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 to give 1-chloro-3-(3-fluoro-4-methoxyphenyl)-6-methoxyisoquinoline (933 mg, 95% yield). δ ppm 1H NMR (400 MHz, CHLOROFORM-d) δ 8.21 (d, J=9.3 Hz, 1H), 7.90-7.87 (m, 1H), 7.86 (s, 1H), 7.81 (s, 1H), 7.27-7.23 (m, 1H), 7.12 (d, J=2.3 Hz, 1H), 7.10-7.04 (m, 1H), 3.98 (d, J=6.0 Hz, 6H); MS: MS m/z 318.1 (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

Sources & evidence

ORD record
ord-787e459a31b2441caa512166ccbf8bb2
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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