Hydrogen Bromide → 5-Bromo-1-chloroisoquinoline

Temperatur

80 °C

To a 500 mL round-bottomed flask containing 1-chloroisoquinolin-5-amine (Step 2, 5.8 g, 32.5 mmol) in H2O (33 mL) and 40% HBr (14 mL) chilled to −50 C in an ice bath, was added a freshly prepared solution of (Sodium nitrate (2.47 g, 35.7 mmol) in 8 mL of H2O) drop-wise over 15 minutes. After the addition, the mixture was kept at 2° C., while stirred an additional 20 minutes. Then urea (0.192 g, 3.2 mmol) was added in order to decompose excess nitrate in the reaction mixture. After an additional 5 minutes of stirring the diazonium salt mixture was transferred into a dropping funnel. The diazonium salt was added drop-wise into a heated (70° C.) solution of Copper (1) Bromide (4.66 g, 32.5 mmol) in 40% HBr (30 mL)). After the addition, the mixture was heated to 80° C. for 1.5 hours. Then the mixture was allowed to cool to ambient temperature. The solid, which had formed in the reaction mixture, was collected by filtration. Then recrystallized from hot EtOAc and Hexanes, after drying, gave a brown crystalline solid, which was titled product (4.576 g; 18.9 mmol). MS (ESI pos. ion) m/z: 243 (M+H). Calc'd Exact Mass for C9H5BrCl: 242.5

1. temperaturechilled to −50 C in an ice bath
2. additionAfter the addition
3. customwas kept at 2° C.
4. customwas transferred into a dropping funnel
5. additionAfter the addition
6. temperatureto cool to ambient temperature
7. customThe solid, which had formed in the reaction mixture
8. filtrationwas collected by filtration
9. customThen recrystallized from hot EtOAc and Hexanes
10. customafter drying
11. customgave a brown crystalline solid, which

ORD-Eintrag

ord-a7dbc53bee154fc9ac9019b586f9928a

Quelldatensatz

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08017601B2