Methyl iodide → 5-(3-chlorophenoxy)-3-iodo-2-methyl-2H-indazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(3-chlorophenoxy)-3-iodo-1H-indazole (194 mg, 524 μmol) in THF (5 mL) at 0° C. was added KOtBu (82.2 mg, 733 μmol) and the mixture stirred at 0° C. for 30 min. MeI (104 mg, 45.8 μL, 733 μmol) was added. The reaction mixture was stirred at 0° C. for 30 min then warmed to 25° C. and stirred for 1.5 h. The reaction mixture was quenched with saturated ammonium chloride in water and extracted with dichloromethane. The combined organics were dried over MgSO4 and concentrated to a clear oil, then purified by chromatography (40 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 20 min) to afford the desired less polar 5-(3-chlorophenoxy)-3-iodo-1-methyl-1H-indazole (154 mg, 400 mmol, 77%) as a clear yellow oil. MS (M+H)+=384.8; 1H NMR (CDCl3) δ: 7.38 (d, J=9.1 Hz, 1H), 7.17-7.29 (m, 2H), 7.11 (d, J=2.3 Hz, 1H), 7.06 (dt, J=7.9, 0.9 Hz, 1H), 6.94 (t, J=2.3 Hz, 1H), 6.86 (dd, J=8.3, 2.3 Hz, 1H), 4.12 (s, 3H). The regioisomer, 5-(3-chlorophenoxy)-3-iodo-2-methyl-2H-indazole, (32 mg, 83.2 μmol, 16%) was also obtained as a clear yellow oil.

Provenance & Evidence