Acetic Anhydride → 4-bromo-1H-indazole

To a solution of 3-bromo-2-methyl aniline (5.0 g, 26.9 mmol) in chloroform (50 mL) was added potassium acetate (1.05 eq., 28.2 mmol, 2.77 g). Acetic anhydride (2.0 eq., 53.7 mmol, 5.07 mL) was added with concurrent cooling in ice-water. The mixture was then stirred at room temperature for 10 minutes after which time a white gelatinous solid formed. 18-Crown-6 (0.2 eq., 5.37 mmol, 1.42 g) was added followed by iso-amyl nitrite (2.2 eq., 59.1 mmol, 7.94 mL) and the mixture was heated under reflux for 18 h. The reaction mixture was allowed to cool, and was partitioned between chloroform (3×100 mL) and saturated aqueous sodium hydrogen carbonate (100 mL). The combined organic extracts were washed with brine (100 mL), separated and dried (MgSO4). The crude product was evaporated onto silica and purified by chromatography eluting with 20% to 40% EtOAc-petrol to give 1-(4-bromo-indazol-1-yl)-ethanone A (3.14 g, 49%) as an orange solid, and 4-bromo-1H-indazole B (2.13 g, 40%) as a pale orange solid. A: 1H NMR (400 MHz, CDCl3) 2.80 (3H, s), 7.41 (1H, t, J=7.8 Hz), 7.50 (1H, d, J=7.8 Hz), 8.15 (1H, s), 8.40 (1H, d, J=7.8 Hz). B: 1H NMR (400 MHz, CDCl3) 7.25 (1H, t, J=7.3 Hz), 7.33 (1H, d, J=7.3 Hz), 7.46 (1H, d, J=7.3 Hz), 8.11 (1H, s), 10.20 (1H, br s).

1. customformed
2. temperaturethe mixture was heated
3. temperatureunder reflux for 18 h
4. temperatureto cool
5. customwas partitioned between chloroform (3×100 mL) and saturated aqueous sodium hydrogen carbonate (100 mL)
6. washThe combined organic extracts were washed with brine (100 mL)
7. customseparated
8. dry with materialdried (MgSO4)
9. customThe crude product was evaporated onto silica
10. custompurified by chromatography
11. washeluting with 20% to 40% EtOAc-petrol

ORD-Eintrag

ord-af5771ba6556495389b91e705ec6da8e

Quelldatensatz

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08883799B2