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

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

Reactant 2

HCID 24813Phosphorus oxychloride

HCID 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

concentrationThe reaction mixture was concentrated
dissolutionThe residue was dissolved in DCM
customThe organic phase was collected
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-4ee6c1ae65fa4e989a96ef2946588207
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957203B2

Reaction notes

Loading…