5-Fluoro-2-iodo-4-methyl-phenylamine synthesis

Yield:1126423-32-2 95%

Reaction Conditions:

with N,N,N-trimethylbenzenemethanaminium dichloroiodate;calcium carbonate in methanol;dichloromethane at 0 - 20; for 17 h;

Steps:

12.1

Example 12; Preparation of Compound 160, 161 and 162; Step 1 - Synthesis of Compound 12B ; 12A 12B; 3-Fluoro-4-methylaniline (94.5 g, 755 mmol), dichloromethane (3 L), and methanol (1 L) were charged into a 5000 ml three-necked flask equipped with mechanic stirrer. The resulting solution was cooled to 0 ⁰C using an ice-water bath and to the cooled solution was added calcium carbonate powder (151 g, 1509 mmol) followed by iodate salt 12A (275 g, 790 mmol). The resulting suspension was maintained at ~ 0 ⁰C for 2 hours then the cool bath was removed and the reaction mixture warmed to room temperature while stirring for an additional 15 hours. The reaction mixture was then filtered and the filtrate was concentrated in vacuo. The resulting residue was dissolved in dichloromethane (1 L), washed sequentially with water (500 mL), saturated sodium carbonate solution (500 mL) and water (500 mL), then dried over sodium sulfate, filtered and concentrated in vacuo. The resulting brown oil residue was dried under house vacuum to provide compound 12B (179 g, 95% yield, >90% purity by NMR) which was used without further purification.

References:

WO2009/32124,2009,A1 Location in patent:Page/Page column 168-169