Phosphorus oxychloride → 1-Chloro-3-(3-fluoro-4-methoxyphenyl)-6-methoxyisoquinoline
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]=1Participants
3
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).