Allyl bromide → 2-(4-Fluorophenyl)pent-4-enoic acid

Participants

Reaction Conditions

Reaction Steps

Step AA (1): NaHMDS (1.0 M in THF, 46.7 mL, 46.7 mmol) was added to a stirred solution of 2-(4-fluorophenyl)acetic acid (3.6 g, 23.4 mmol) in THF (50 mL) at 0° C. The resulting mixture was stirred for 20 min at 0° C. and neat 3-bromoprop-1-ene (2.02 mL, 23.4 mmol) was added. The mixture was allowed to warm to rt. After 16 hr, the reaction was quenched with water (3 mL). The crude mixture was concentrated in vacuo. Aqueous NaOH (1 M, 150 mL) was added to the residue and the resulting mixture was extracted with Et2O (2×100 mL). The basic layer was acidified with aqueous HCl (1 M, 200 mL) and the resulting solution was extracted with Et2O (2×100 mL). The combined organic layers from the acidic extraction were washed with mixture of brine/1N HCl/sodium sulfite, dried (MgSO4), filtered, and concentrated in vacuo. The residue was dissolved in toluene (˜50 mL) and left to sit at rt for 3 days. A white solid was collected by vacuum filtration. The solid was dried under high vacuum to afford 2-(4-fluorophenyl)pent-4-enoic acid (2.03 g, 10.1 mmol, 43% yield) as an off-white crystalline solid. 1H NMR (500 MHz, chloroform-d) δ ppm 7.28-7.34 (m, 2 H) 6.99-7.07 (m, 2 H) 5.71 (dddd, J=17.09, 10.22, 6.87, 6.71 Hz, 1 H) 5.08 (dd, J=17.09, 1.53 Hz, 1 H) 5.01-5.05 (m, 1 H) 3.65 (t, J=7.63 Hz, 1 H) 2.75-2.87 (m, 1 H) 2.52 (dt, J=14.27, 7.06 Hz, 1 H).

Provenance & Evidence