Cyclohexanol → (5-Cyclohexyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetic acid ethyl ester

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Reaction Steps

To a mixture of (5-hydroxy-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetic acid ethyl ester (8.0 g) in anhydrous tetrahydrofuran (160 ml) was added cyclohexanol (3.2 g), diethylazadicarboxylate (6.9 g) and then triphenyl phosphine (12.6 g). Resulting mixture was stirred at room temperature overnight and concentrated. Residue was partitioned between water and ethyl acetate. Aqueous layer was extracted with ethyl acetate. Combined organic layers were washed with brine, dried over magnesium sulfate and filtered. Filtrate was concentrated and purified by silica gel chromatography (eluting with 5% ethyl acetate in methylene chloride) to give the title compound (6.2 g). 1H NMR (200 MHz, CDCl3) δ 7.73 (dd, J=8.2, 0.8 Hz, 1 H), 7.30 (br s, 1 H), 7.12 (m, 1 H), 4.38 (m, 3 H), 4.21 (q, J=7.1 Hz, 2 H), 2.02 (m, 2 H), 1.82-1.25 (m, 13H).

Provenance & Evidence