Ethylene Glycol → 1,3-Dioxolane, 2-[3-fluoro-4-(phenylmethoxy)phenyl]-2-methyl-

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Reaction Steps

A mixture of 1-(4-(benzyloxy)-3-fluorophenyl)ethanone 22 (23.8 g, 97.5 mmol), ethylene glycol (16.4 mL, 293 mmol), p-TsOH (930 mg, 4.88 mmol) and toluene (400 mL) was stirred under reflux conditions for 4 days, azeotropically removing water with a Dean-Stark trap. The mixture was cooled to room temperature and quenched by addition of saturated sodium bicarbonate solution (200 mL). The aqueous phase was back-extracted with toluene (3×200 mL). The combined organic phases were washed with brine (200 mL), dried over sodium sulfate, filtered and the solvent removed under reduced pressure to give 28.7 g (103%) of crude 23 as a yellow solid. Crude 23 was used without further purification. 1H NMR (CDCl3) δ: 7.39 (m, 5H), 7.22 (dd, 1H), 7.16 (dd, 1H), 6.95 (t, 1H), 5.12 (s, 2H), 4.12 (dd, 2H), 3.77 (dd, 2H), 1.62 (s, 3H). LCMS m/z=289.1 (M+H).

Provenance & Evidence