N-[3,5-Dichloro-4-(6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-benzamide synthesis

Yield:1581304-48-4 91%

Reaction Conditions:

Stage #1: 3,5-dichloro-4-((6-chloropyridazin-3-yl)oxy)aniline;benzoic acid anhydridewith glacial acetic acid at 100; for 0.583333 h;Large scale;
Stage #2: with anhydrous Sodium acetate at 110; for 14.5 h;Large scale;Reagent/catalyst;Solvent;Temperature;

Steps:

1 Example 1

The crude 2 above was taken up in acetic acid (1.48 L, 7.5 vol) and benzoic anhydride (168 g, 0.741 mol, 1.1 equiv) was added. The resulting mixture was heated to 100 °C and after 35 min at that temperature, the amount of 2 was 0.8%. Sodium acetate (110 g, 2 equiv) was added and the temperature increased to 110 °C. After 14.5 h at that temperature, HPLC analysis of the reaction mixture showed no intermediate remaining, and the reaction was deemed complete. The batch was cooled to 75 °C and water (1.5 L, 7.7 vol) was added over a period of 1 hour while maintaining a batch temperature between 72-75 °C. The batch was cooled to 21 °C and filtered through Sharkskin filter paper. The reactor and cake were washed sequentially with water (1 L, 5 vol). After drying the collected solid in a 50 °C vacuum oven for 16 h, the yield of crude 4 was 195 g (77%). HPLC analysis (Method B, 220 nm) showed a purity of 91.6%.

References:

WO2014/43706,2014,A1 Location in patent:Page/Page column 25; 26; 43; 44; 53; 54; 55