Iodoethane → 6-chloro-1-ethyl-3-iodo-1H-indazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-3-iodo-1H-indazole (913 mg, 3.28 mmol) in THF (12 ml) at 0° C. was added KOt-Bu (429 mg, 3.82 mmol). The reaction mixture was stirred at 0° C. for 30 min then added iodoethane (0.37 ml, 4.6 mmol). Stirred at 0° C. for 30 min then warmed to room temperature and stirred for 48 h. The reaction was quenched with water and extracted with EtOAc (2×). The combined organics were washed with brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 10% to 50% EtOAc/heptane to afford 622 mg (62%) of 6-chloro-1-ethyl-3-iodo-1H-indazole as a white powder. 1H NMR (CDCl3, 300 MHz): δ (ppm) 7.37-7.43 (m, 2H), 7.17 (dd, J=8.7, 1.1 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.51 (t, J=7.2 Hz, 3H). Also isolated 174 mg (17%) of 6-chloro-2-ethyl-3-iodo-2H-indazole as a more polar, minor regioisomer. 1H NMR (CDCl3, 300 MHz): δ (ppm) 7.66-7.70 (m, 1H), 7.35 (d, J=9.1 Hz, 1H), 7.04-7.12 (m, 1H), 4.56 (q, J=7.2 Hz, 2H), 1.58 (t, J=7.2 Hz, 3H).

Provenance & Evidence