Methyl iodide → 3-iodo-1-methyl-4,5,6,7-tetrahydro-1H-indazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-iodo-4,5,6,7-tetrahydro-1H-indazole (674 mg, 2.72 mmol) in THF (10 mL) at 0° C. was added KOtBu 1M in THF (3.8 mL, 3.8 mmol) and the mixture stirred at 0° C. for 30 min where it became a brown-reddish solution then added MeI (540 mg, 238 μL, 3.8 mmol). The reaction mixture was stirred at 0° C. for 30 min then warmed to 25° C. and stirred for 18 h. The reaction mixture was quenched with saturated ammonium chloride in water and extracted with dichloromethane (3×30 mL), organics dried over MgSO4 and concentrated to an off-white solid. Then dissolved in toluene and purified by chromatography (115 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 15 min to afford the more polar desired 3-iodo-1-methyl-4,5,6,7-tetrahydro-1H-indazole (570 mg, 2.17 mmol, 80.0%) as an off-white solid. MS (M+H)+=263 (100% purity); 1H NMR (CDCl3) δ: 3.72 (s, 3H), 2.42-2.72 (m, 2H), 2.30 (t, J=6.0 Hz, 2H), 1.56-1.93 (m, 4H). The regioisomer 3-iodo-2-methyl-4,5,6,7-tetrahydro-2H-indazole (182 mg, 694 μmol, 25.6%) as also obtained as a white solid.

Provenance & Evidence