Yield:886762-67-0 75%

Reaction Conditions:

Stage #1: 4-amino-3-(trifluoromethoxy)benzoic acidwith hydrogenchloride;water;sodium nitrite at 0; for 0.333333 h;
Stage #2: with potassium iodide in water at 0; for 3 h;

Steps:

4-Iodo-3-(trifluoromethoxy)benzoic acid (44)

General procedure: To a solution of 42 (200 mg, 0.9 mmol) in H₂O (2 mL) and HCl 37% (2 mL) at 0°C, was slowly added a solution of NaNO₂ (70 mg, 1.0 mmol) in H₂O (2 mL). The solution obtained was then stirred for 20 minutes and then added at 0°C to a solution of KI (520 mg, 3.15 mmol) in H₂O (2 mL). The mixture was stirred for 3 hours. After cooling in an ice-water bath, the solid was filtered off. The filtrate was diluted with EtOAc, washed with 10% sodium methabisulphite, dried over anhydrous Na₂SO₄ and concentrated to give 225 mg of 44 (75% yield) as a white solid.

References:

Caldarelli, Marina;Angiolini, Mauro;Disingrini, Teresa;Donati, Daniele;Guanci, Marco;Nuvoloni, Stefano;Posteri, Helena;Quartieri, Francesca;Silvagni, Marco;Colombo, Riccardo [Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,# 15,p. 4507 - 4511] Location in patent:supporting information; experimental part