Benzenamine, 4-(difluoromethoxy)-2-iodo- synthesis

Yield:1000801-26-2 22%

Reaction Conditions:

with Iodine monochloride in acetic acid at 60 - 85; for 1.5 h;

Steps:

20

INTERMEDIATE 202-Iodo-4-difluoromethoxyanilineA solution of 4-(difluoromethoxy)aniline (1.0 g, 6.30 mmol) in AcOH (6 mL) was heated to 60⁰C and iodine monochloride (1.07 g, 6.6 mmol) in AcOH (15 mL) was added dropwise. The reaction mixture was then heated to 85°C and stirred for 1.5 h. The reaction mixture was cooled to r.t. and poured into cold water and the resulting suspension filtered. The filtrate was concentrated in vacuo to give a dark brown oil. Purification by column chromatography (SiO₂, 10-20% EtOAc/hexanes) gave the title compound (0.40 g, 22%) as a dark brown oil. δ_H (DMSO-d₆) 7.38 (IH, d, J 2.7 Hz), 6.98- 6.94 (IH, m), 6.97 (IH, t, J74.8 Hz), 6.75 (IH, d, J 8.8 Hz), 5.20 (2H, br. s). LCMS (ES+) 286.0 (M+H)⁺, RT 3.28 minutes (Method 5).

References:

WO2009/1089,2008,A1 Location in patent:Page/Page column 30