Ethanol → 4-Bromo-5-fluoro-isoquinoline

Temperatur

0 °C

5-Amino-4-bromo-isoquinoline (see Gordon et al., J. Heterocycl. Chem., 4, 1967, 410-411) (1.86 g, 8.34 mmol) was stirred in 48% fluoroboric acid (15 mL)/EtOH (15 mL) until completely dissolved. The solution was cooled to 0° C., and sodium nitrite (660 mg, 9.59 mmol) in H2O (1 mL) was added dropwise. The solution was diluted with Et2O (30 mL), and the tan diazonium fluoroborate salt was collected by filtration and dried under vacuum. The solid was placed in a flask and carefully heated over a flame to expel nitrogen. The dark brown residue was diluted with 10% NaOH and extracted with chloroform. Organics were washed with brine, dried over MgSO4, and concentrated in vacuo. Purification by silica gel chromatography (40% to 50% ethyl acetate/hexanes) gave 798 mg (42%) of 4-bromo-5-fluoro-isoquinoline as a white solid. 1H NMR (300 MHz, CDCl3) δ9.36 (d, 1H, J=2.4 Hz), 8.74 (s, 1H), 8.07-8.11 (m, 1H), 7.70-7.80 (m, 2H). Anal. (C9H5BrFN) C, H, N.

1. dissolutionuntil completely dissolved
2. filtrationthe tan diazonium fluoroborate salt was collected by filtration
3. customdried under vacuum
4. customThe solid was placed in a flask
5. temperaturecarefully heated over
6. temperaturea flame
7. additionThe dark brown residue was diluted with 10% NaOH
8. extractionextracted with chloroform
9. washOrganics were washed with brine
10. dry with materialdried over MgSO4
11. concentrationconcentrated in vacuo
12. customPurification by silica gel chromatography (40% to 50% ethyl acetate/hexanes)

ORD-Eintrag

ord-3712dcbc065f4ac4a3fda89c6b3f65e6

Quelldatensatz

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06555539B2