1H-Isoindole-1,3(2H)-dione, 2-[2-(1H-1,2,3-triazol-1-yl)ethyl]- synthesis

Yield:4396-77-4 34%

Reaction Conditions:

with caesium carbonate in N,N-dimethyl-formamide at 0 - 21;

Steps:

111

Add lH-l,2,3-triazole (250 g; 3.51 mol), N-(2-bromoethyl) phthalimide (942 g; 3.52 mol) and 1500 mL of DMF to a 5-L roundbottom flask fitted with a mechanical stirrer, nitrogen inlet and temperature probe. Cool the mixture to 15 ⁰C. Stir the mixture until all of the solids are nearly dissolved and then cool in an ice- water bath. Add cesium carbonate (1145 g; 3.51 mol) in portions over 10 min. The reaction mixture exotherms to 21 ⁰C. Allow the mixture to stir and come to RT overnight. Pour the reaction mixture into a 12-L flask containing 8 L of ice-water. Stir the suspension for 30 min and then filter and rinse the solid with 3 L of water. Air-dry for 2 h. Recrystallize the mixture of regioisomers from 7 L of absolute ethanol. Isolate the solid by filtration and air-dry. Recrystallize again from 16 L of absolute ethanol. Isolate the solids by filtration and rinse with fresh ethanol (1000 mL). Vacuum-dry the solids at 40 ⁰C to give the title compound, 292.7 g (34 %) as a white solid. MS (EI) m/z 243 [M+lf.

References:

WO2008/144223,2008,A2 Location in patent:Page/Page column 36; 37