Hydrochloric Acid → 1-Iodo-3-methoxy-5-(trifluoromethyl)benzene

Participants

Reaction Steps

A solution of conc. HCl in H20 (1:1 v/v, 1.1 ml) was added to a solution of 3-methoxy-5-(trifluoromethyl)benzenamine (250 mg, 1308 μmol) in THF (2 ml). The mixture was stirred at RT for 1 hr and then cooled to 0 C. A chilled solution of sodium nitrite (208 mg, 3008 μmol) in H20 (2 ml) was added slowly. Additional H20 (0.8 ml) was added. A solution of potassium iodide (369 mg, 2223 μmol) in H20 (0.415 ml) was added dropwise. Additional H20 (0.62 ml) and THF (3.9 ml) was added and the reaction mixture was then gradually warmed to room temperature and stirred overnight. Analysis by LCMS indicated the reaction was complete. Saturated aqueous Na2CO3 was added, the volatiles were removed by rotovap, and the mixture was partitioned with DCM. The aqueous layer was extracted with DCM (2×), the organic layers were combined and washed with brine and dried over Na2SO4. Purification by Biotage was performed using 100% Hexanes to give a clear oil (208 mg, 53% yield).

Provenance & Evidence