Potassium Carbonate → 4,5-diiodo-2-cyclopropyl-1-methyl-1H-imidazole

Participants

Reaction Conditions

Reaction Steps

4-Iodo-2-cyclopropyl-1-methyl-1H-imidazole, 5k′. To a solution of 2-cyclopropyl-1-methyl-1H-imidazole (4a) (5.5 g, 45.0 mmol) in isopropyl acetate (110 mL) was added K2CO3 (1.25 g, 9.0 mmol) followed by NIS (40.3 g, 179.1 mmol) in portions over 2 h. The solution was stirred at 75° C. for 3 h, allowed to cool to room temperature and quenched with a 10% aqueous solution of K2CO3. The organic layer was washed with 10% K2CO3. The combined organic layers were concentrated affording crude 4,5-diiodo-2-cyclopropyl-1-methyl-1H-imidazole (10.5 g) as a dark solid. A solution of the resulting solid in THF (100 mL) was cooled to −20° C. and treated with 2 M i-PrMgCl in THF (17.5 mL, 35.0 mmol) dropwise. The reaction mixture was quenched with water and filtered. The organic layer was washed with brine and water, and concentrated afford 5k′ (8.64 g, 77% yield) as a dark orange oil. 1H-NMR (400 MHz, CDCl3) δ 6.85 (s, 1H), 3.66 (s, 3H), 1.74 (dt, J=8.4, 5.2 Hz, 1H), 1.03-0.91 (m, 4H); 13C-NMR (100 MHz, CDCl3) δ 151.9, 125.8, 79.1, 32.5, 6.9, 6.8.

Provenance & Evidence