N-Hydroxyphthalimide → 2-((1H-imidazol-2-yl)methoxy)isoindoline-1,3-dione

Participants

Reaction Steps

To an ice-cold solution of (1H-imidazol-2-yl)methanol hydrochloride (2.0 g, 15 mmol), N-hydroxyphthalimide (2.4 g, 15 mmol) and triphenylphosphine (4.0 g, 15 mmol) in THF (65 mL) was added a solution of diethyl azodicarboxylate (2.6 mL, 16 mmol) in THF (10 mL) dropwise. The stirred reaction mixture was allowed to warm to ambient temperature. After 1 day, most of the THF was removed under reduced pressure. The residue was partitioned between CH2Cl2 (75 ml) and H2O (30 mL). The organic layer was separated and washed with saturated NaHCO3 (75 mL) and saturated NaCl (20 ml), dried (Na2SO4) and concentrated under reduced pressure. Purification by column chromatography (silica gel, CH2Cl2 to 95:5 CH2Cl2/MeOH) gave 2-(1H-imidazol-2-ylmethoxy)-1,3-dihydro-2H-isoindole-1,3-dione (240 mg, 6.5%) which was used directly in the next reaction.

Provenance & Evidence