Hydrochloric Acid → 4-Bromo-8-chloroisoquinoline

Temperatur

80 °C

To a solution of 8-chloroisoquinoline (1.0 g, 6.1 mmol) in nitrobenzene (20 mL) at 180° C. was added bromine (0.35 mL, 6.7 mmol) over 10 min. Heating and stirring were continued for 2 hours. The mixture was allowed to cool to about 80° C., then 2M HCl in Et2O (5 mL) was added, followed by Et2O (5 mL) and hexanes (60 mL). The resulting slurry was filtered, washed with hexane and dried. The collected solid was dissolved in water, then the solution was adjusted to pH 9 with Na2CO3 (aq). The solution was extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography eluting with 0-20% EtOAc/hexanes to afford the title compound as a white solid: 1H NMR (500 MHz, CDCl3): δ 9.62 (s, 1H); 8.83 (s, 1H); 8.13 (t, J=5.0 Hz, 1H); 7.74 (d, J=5.0 Hz, 2H). LC6: 4.08 min, (M+H): 242.

1. temperatureHeating
2. filtrationThe resulting slurry was filtered
3. washwashed with hexane
4. customdried
5. dissolutionThe collected solid was dissolved in water
6. extractionThe solution was extracted with EtOAc
7. dry with materialThe organic layer was dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by silica gel chromatography
11. washeluting with 0-20% EtOAc/hexanes

ORD-Eintrag

ord-1c6fa6a2a9894d06b81f488f83d2ff5d

Quelldatensatz

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08436015B2