4-Fluorophenol → HCID 13831434, compound

Participants

Reaction Conditions

Reaction Steps

Under argon, 100 g (0.892 mol) of 4-fluorophenol (2) was combined with 105.2 g (0.892 mol) of (S)-ethyl lactate and 233.8 g (0.892 mol) of triphenylphosphine in 1200 mL of tetrahydrofuran (THF). The reaction mixture was cooled to −5° C., and 180.4 g (0.892 mol) of diisopropylazodicarboxylate (DIAD) in 500 ml of THF was dropwise added. The ice bath was removed, and stirring was continued at room temperature for 18-22 hr. THF was then evaporated in vacuo, and 1400 mL of hexane-ether (80:20) was added to the residue, and the remaining solid was removed by filtration. The filtrate was then washed with 2×600 mL of 1N NaOH, followed by 2×600 mL of water and 600 mL of brine. The washed filtrate was then dried over MgSO4, filtered and then evaporated to give 185 g of (R)-ethyl-2-(4-fluorophenoxy)-propionate, 7, as a light yellow oil in 98% yield, Bp 80° C. at 0.7 mm Hg. The reaction is shown as follows:

Provenance & Evidence