Yield: 75%

Reaction Conditions:

Stage #1:3-bromo-4-chloroaniline with sulfuric acid at 20; for 0.5 h;
Stage #2: with sodium nitrite in water at -5;
Stage #3: with Oxalamide;potassium iodide in water;ethyl acetate at -5;

Steps:

6.6B.2 Step 2:
A solution of 3-bromo-4-chloro-phenylamine (10.3 g, 50 mmol) in 25 % H2SO4 (200 mL) was stirred at rt for 30 min then cooled to - 5 °C and a solution of sodium nitrite (4.2 g, 60 mmol) in water (50 mL) was added dropwise. After the addition, the mixture was then kept stirred at the same temperature for 1 h and then oxalamide (1.0 g) was added. The mixture was then kept stirred for another 10 min then added dropwise to a solution of potassium iodide (12.5 g, 75 mmol, 1.5 eq) in EtOAc (150 mL) and water (100 mL) while keeping the inner temperature below - 5 °C. The mixture was extracted with EtOAc, and the organic layers were washed with saturated sodium bisulfate solution and brine consequently and then dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via flash- chromatography on silica gel (10 % EtOAc in petroleum ether) to give 2-Bromo-l-chloro -4- iodo-benzene (1 1.8 g, 75 %) as yellow solid. MS ESI calc'd. For C₆H₃BrClI [M + H]⁺ 319, found 319.

References:

MERCK SHARP & DOHME CORP.;ANDRESEN, Brian, M.;ANTHONY, Neville, J.;MILLER, Thomas, A. WO2014/74422, 2014, A1 Location in patent:Paragraph 00184