Tetrafluoroboric acid → 5-Bromo-8-fluoroisoquinoline

Temperatur

0 °C

To a solution of 8-amino-5-bromoisoquinoline in 48% HBF4 (30 mL) at 0° C. was slowly added an aqueous (10 mL) solution of NaNO2 (172 mg, 2.5 mmol). The reaction mixture was stirred at 0° C. for 1 h and was then concentrated under reduced pressure to give a dark residue. The dark residue was heated to 150° C. for 16 h. The resulting dark oil was cooled to 23° C., quenched with ammonium hydroxide and extracted with DCM. The organic solution was concentrated and the resulting dark solid was recrystallized from EtOAc/Hexanes. The desired product (100 mg) was in the mother liquor while the by-product was filtered away as a solid. LCMS showed an m/z of 228.0/226.0 with a retention time of 1.318 min, method [1].

1. concentrationwas then concentrated under reduced pressure
2. customto give a dark residue
3. temperatureThe dark residue was heated to 150° C. for 16 h
4. temperatureThe resulting dark oil was cooled to 23° C.
5. customquenched with ammonium hydroxide
6. extractionextracted with DCM
7. concentrationThe organic solution was concentrated
8. customthe resulting dark solid was recrystallized from EtOAc/Hexanes
9. filtrationwas filtered away as a solid

ORD-Eintrag

ord-78428fdd9fa9456296697c314a7b9129

Quelldatensatz

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09073891B2