Reaktion #1939289

Reaktionsgleichung

6-fluoro-4-methoxyisoquinolin-1-ol

POCl3

→

1-chloro-6-fluoro-4-methoxyisoquinoline

Ausbeute 69.3%

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction mixture was concentrated
2. 2
   workup.DISSOLUTIONThe residue was dissolved in DCM
3. 3
   SonstigeThe organic phase was collected
4. 4
   Trocknendried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated under vacuum
7. 7
   SonstigeThe crude material was purified by silica gel chromatography
8. 8
   SonstigeThe product fractions were collected
9. 9
   Sonstigethe solvent removed under vacuum

Vorschrift

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).

Quelle