N-Hydroxyphthalimide → [cis-2-[[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]methyl]-1-(4-methoxyphenyl)-4-oxo-3-azetidinyl]carbamic acid 1,1-dimethylethyl ester

Participants

Reaction Steps

To a mixture of cis-2-hydroxymethyl-1-(4-methoxyphenyl)-4-oxo-3-azetidinyl-carbamic acid 1,1-dimethylethyl ester (5.8 g, 18 mmol), N-hydroxyphthalimide (3.0 g, 18 mmole) and triphenylphosphine (5.7 g, 22 mmol) was added diethyl azodicarboxylate (3.7 g, 21 mmol). The reaction was allowed to stir at room temperature for 0.5 hours whereby the solvent was removed in vacuo. The reaction mixture was dissolved in methylene chloride and again the solvent evaporated to remove any residual THF. A solid precipitates and is washed with a solution of methylene chloride-diethyl ether (1:1). The filtrate is concentrated and the solid precipitate is again washed with a solution of methylene chloride-diethyl ether (1:1) and combined with the previously recovered material to afford 5.0 g of [cis-2-[[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]methyl]-1-(4-methoxyphenyl)-4-oxo-3-azetidinyl]carbamic acid 1,1-dimethylethyl ester (59%). Another 1.9 g (22.3%) of product could be recovered after concentration of the filtrate followed by flash chromatography (ethyl acetate-hexane, 1:9): mp 188°-189° C.; IR (KBr) 3435, 2980, 1795, 1735, 1710, 1500, 1390, 1370, 1160, and 1130 cm-1 ; NMR(CDCl3) δ 1.48 (9H, s), 3.74 (3H, s), 4.40 (1H, br d, J=12 Hz), 4.52 (1H, m), 4.98 (1H, br d, J=12 Hz), 5.44 (1H, m), 6.22 (1H, d, J-9 Hz, exchangeable), 6.82 (2H, d, J=8 Hz), 7.43 (2H, d, J=8 Hz), 7.78 (4H, m).

Provenance & Evidence