Sodium Carbonate → 6-Bromo-3-fluoroisoquinoline

Temperature

-78 °C

To a mixture of 6-bromoisoquinolin-3-amine (0.71 g, 3.18 mmol) in pyridine hydrofluoride (10 mL, 3.18 mmol) at −78° C. was carefully added sodium nitrite (0.26 g, 3.82 mmol). The reaction mixture was stirred at −78° C. for 5 minutes. The reaction mixture was then warmed to room temperature over 40 minutes. The mixture was poured into an ice bath and the pH was adjusted to >9 with Na2CO3. The mixture was filtered to recover a yellow-purple solid. The solid was dissolved in EtOAc and water with stirring. The mixture was extracted with EtOAc (3×200 mL). The EtOAc was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was taken up in DCM-MeOH and adsorbed onto silica gel. Purification by chromatography on silica gel eluting with EtOAc 0-7% in hexanes provided the product (500 mg, 70%). LCMS (API-ES) m/z: 226, 228 (M+H+).

1. temperatureThe reaction mixture was then warmed to room temperature over 40 minutes
2. additionThe mixture was poured into an ice bath
3. filtrationThe mixture was filtered
4. customto recover a yellow-purple solid
5. dissolutionThe solid was dissolved in EtOAc
6. stirringwater with stirring
7. extractionThe mixture was extracted with EtOAc (3×200 mL)
8. washThe EtOAc was washed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customPurification by chromatography on silica gel eluting with EtOAc 0-7% in hexanes

ORD record

ord-9456857d05734ff5814045b1fcacfc82

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07897619B2