Hydrochloric Acid → N-(4-chloro-2-fluoro-3-iodophenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(4-chloro-2-fluorophenyl)acetamide prepared above (12.0 g, 64 mmol) in THF (300 mL) at −78° C. is added dropwise n-BuLi (2.0 M in cyclohexane, 64 mL, 128 mmol) keeping the reaction temperature below −60° C. The reaction mixture is stirred between −60 to −70° C. for 2 hours and 1,1,1-trifluoro-2-iodoethane (20.1 g, 96 mmol) is added dropwise at −78° C. The mixture is stirred at this temperature for additional 3 hrs. Then a 1N HCl (200 mL) solution is added slowly at −78° C. The mixture is allowed to warm to room temperature and extracted with EtOAc (200 mL×3). The combined organic layers are washed with water and brine, then dried over MgSO4. The solvent is removed and the residue is stirred in ether and hexanes (1:2, 120 mL) for 1 hour. The solid is filtered to give N-(4-chloro-2-fluoro-3-iodophenyl)acetamide.

Provenance & Evidence