Cyclobutanone → 1-(4-Fluorophenyl)-2-(1-hydroxycyclobutan-1-yl) ethan-1-one

Participants

Reaction Steps

Under nitrogen, 11.0 g (100 mmol) of titanium(IV) chloride in 140 mL of methylene chloride at 0° C. was slowly treated with a solution of 8.2 mL (110 mmol) of cyclobutanone in 30 mL of methylene chloride prior to the dropwise addition of a solution of 21.1 g (100 mmol) of 1-fluoro-4-[1[(trimethylsilyl)oxy]ethenyl]benzene (obtained from Step 2) in 15 mL of methylene chloride. The reaction was stirred for 15 minutes and then poured into 200 mL of ice/water; the phases were separated. The aqueous phase was extracted twice with 30 mL of methylene chloride and combined with the original methylene chloride phase. The combined extracts were washed 3 times with 120 mL of saturated sodium carbonate/water (1:1) and once with brine, dried (MgSO4), and concentrated in vacuo to give 20.4 g (98%) of crude 1-(4-fluorophenyl)-2-(1-hydroxycyclobutan-1-yl) ethan-1-one as an oil: NMR (CDCl3) δ 1.53-1.70 (m, 1H), 1.80 -1.94 (m, 1H), 1.99-2.10 (m, 2H), 2.17-2.31 (m, 2H), 3.31 (s, 2H), 7.10-7.19 (m, 2H), 7.95-8.03 (m, 2H).

Provenance & Evidence