N-Hydroxyphthalimide → 2-(tetrahydro-2H-pyran-4-yloxy)-1H-isoindole-1,3(2H)-dione

Participants

Reaction Steps

A light suspension containing N-hydroxylphthalimide (18.4 mmol, 3.0 g), triphenylphosphine (18.4 mmol, 4.82 g), tetrahydro-4H-pyran-4-ol (18.4 mmol, 1.75 mL) and anhydrous THF (50 mL), were transferred to a flask containing di-tert-butyl azodicarboxylate (20.2 mmol, 4.66 g) under nitrogen. Over 2 hours the reaction stirred at room temperature and changed from a dark orange to yellow in appearance. The solvent was removed under vacuum and replaced with trifluoroacetic acetic acid (10 mL). The reaction was stirred for 30 minutes and the TFA was removed under vacuum. The crude residue was then dissolved in ethyl acetate, washed with a saturated aqueous solution of sodium bicarbonate, 5% aqueous solution of potassium carbonate, brine and dried over magnesium sulfate. The solvent was removed under vacuum and the residual triphenylphosphine oxide was crystallized and filtered using hexanes and ether. The solvent was again removed and the crude solid was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and recrystallization using methylene chloride and hexanes providing 1.69 g (37%) of a white crystal. Rf=0.3 (2:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.84-7.82 (2H,m), 7.75-7.73(2H,m), 4.46-4.40 (1H,m), 4.08-4.02 (2H,m), 3.50-3.44 (2H,m), 2.04-1.98 (2H,m), 1.92-1.84 (2H,m).

Provenance & Evidence