Ethanol → 4-Bromo-5-fluoro-isoquinoline

Temperature

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) δ 9.36 (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 record

ord-9945b0499a4b401da5f67120aab76d4b

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07232912B2