Hydrogen Bromide → 5-Bromoisoquinoline

Temperature

-78 °C

5-Aminoisoquinoline (5.0 g, 34.7 mmol) was mixed with 48% aqueous HBr (65 mL) at −78° C. for 15 min. Sodium nitrite (3.1 g, 45 mmol) in water (6 mL) was then added dropwise. After stirring for 15 min at −78° C., the mixture was warmed to 0° C. Copper powder (0.3 g) was added very slowly to avoid excessive foaming. After addition was completed, the reaction vessel was fitted with a reflux condensor and the mixture was heated to 100° C. for 4 h. The mixture was poured onto ice (ca. 200 g) and was made basic (pH=10) with KOH. The aqueous mixture was extracted with ethyl acetate, the combined organic layers were washed with brine, were dried (MgSO4), were filtered, and were concentrated in vacuo. Purification by silica gel chromatography (10:1 hexanes—ethyl acetate) afforded 3.8 g (53% yield) of 5-bromoisoquinoline; 1H NMR (400 MHz, CD3OD) δ9.25 (s, 1H), 8.57 (d, J=6.2 Hz, 1H), 8.1 (m, 3H), 7.60 (m, 1H); MS (AP/Cl): 208.0, 210.0 (M+H)+.

1. temperaturethe mixture was warmed to 0° C
2. additionAfter addition
3. customthe reaction vessel was fitted with a reflux condensor
4. temperaturethe mixture was heated to 100° C. for 4 h
5. additionThe mixture was poured onto ice (ca. 200 g)
6. extractionThe aqueous mixture was extracted with ethyl acetate
7. washthe combined organic layers were washed with brine
8. dry with materialwere dried (MgSO4)
9. filtrationwere filtered
10. concentrationwere concentrated in vacuo
11. customPurification by silica gel chromatography (10:1 hexanes—ethyl acetate)

ORD record

ord-f0060a4cdb894082a90e727ee74dbc5f

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06756385B2