1-Bromo-4-fluorobenzene → 8-(4-Fluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

Participants

Reaction Steps

To a 500 ml round-bottom flask equipped with a mechanical stirrer, condenser and addition funnel were added magnesium turnings (3.50 g, 140 mmol) and enough THF to cover the Mg. A solution of 1-bromo-4-fluorobenzene (12.45 g, 70.43 mmol) in THF (90 ml) was added dropwise at such a rate that the reaction maintained a gentle reflux following reaction-initiation (the initiation may be accomplished by warming the flask). After the mixture was refluxed for an additional 2.5 h, a solution of 1,4-cylohexanedione monoethylene ketal (10.00 g, 64.03 mmol) in THF (75 ml) was added dropwise. The mixture was kept at refluxing for an additional 2 h before being quenched with saturated ammonium chloride solution (7 ml). After removal of the magnesium salts by filtration, the filtrate was concentrated to dryness. The residue was dissolved in CHCl3 and washed with water and brine. The organic layer was separated, dried over MgSO3, and concentrated. The residue was purified by flash chromatography (30% ether in petroleum ether) to afford the desired alcohol (13.50 g, 87%) as a colorless solid. mp 133-134° C. 1H NMR (500 MHz, CDCl3) δ1.69 (d, J=11.7 Hz, 2H), 1.79 (d, J=12.2 Hz, 2H), 2.05-2.18 (m, 4H), (m, 4H), 7.02 (t, J=8.3, 2H), 7.47-7.50 (m, 2H).

Provenance & Evidence