Hydrochloric Acid → 2-[4-(3,4-Dichloro-benzyl)-morpholin-2-ylmethyl]-isoindole-1,3-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(oxiran-2-ylmethyl)-1H-isoindole-1,3(2H)-dione (2 g) in tetrahydrofuran (4 ml) was added 2-[(3,4-dichlorobenzyl)amino]ethanol (2.16 g) with stirring, under a nitrogen atmosphere. The mixture was heated to 66° C. for 22 h, then cooled to 0° C. A further portion of tetrahydrofuran (10 ml) was added, followed by triphenylphosphine (2.88 g). Diisopropyl azodicarboxylate (2.2 g) was then added over 10 min. The mixture was stirred at 0° C. for a further 30 min, and at room temperature for 14 h. To the crude solution was added ethyl acetate (100 ml), then 2M aqueous hydrochloric acid (250 ml). The resulting white precipitate was isolated by filtration, and dried in vacuo to give the title compound as its white crystalline hydrochoride salt (2.01 g). This was partitioned between 8% aqueous sodium bicarbonate (200 ml) and ethyl acetate (50 ml). The organic phase was separated, dried over magnesium sulfate and the solvent evaporated in vacuo to give a solid. Dichloromethane (20 ml) was added to the residue and the solvent again evaporated in vacuo to give the title compound as a white solid (1.1 g).

Provenance & Evidence