Toluene → 2-((S)-2-hydroxy-propoxy)-isoindole-1,3-dione

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To a suspension of N-hydroxyphthalimide (250 g, 1.53 mol), toluene (450 mL), tetrabutylammonium bromide (24.7 g, 76.6 mmol) and (S)-(−)-propylene oxide (214.7 mL, 3.07 mol) was added DIPEA (13.3 mL, 76.6 mmol). The reaction mixture was heated under nitrogen at reflux for 3 hours. The reaction mixture was concentrated in vacuo to obtain a yellow solid. The solid was dissolved in hot ethyl acetate and loaded onto a plug of flash silica (600 g) and the product eluted with diethyl ether (4 L). The ether solution was concentrated in vacuo to yield a pale yellow solid. The solid was dissolved in ethyl acetate (150 mL) at 75° C. and cyclohexane (300 mL) added. The solution was allowed to cool down to room temperature with stirring, causing a white solid to crystallise from the solution. The crystals were collected by filtration, washing with ethyl acetate/hexane (1:2). The solid was recrystallised using the conditions described previously to yield the product as a white crystalline solid (233 g, 69%). 1H NMR (CDCl3, 400 MHz) 7.89-7.83 (2H, m), 7.81-7.75 (2H, m), 4.22 (1H, dd, J=11.5, 2.3 Hz), 4.11-4.02 (1H, m), 3.93 (1H, dd, J=11.3, 9.2 Hz), 3.79 (1H, d, J=3.2 Hz), 1.18 (3H, d, J=6.4 Hz).

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