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

Temperatur

0 °C

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).

1. temperatureto warm to rt
2. waitAfter 16 hr
3. customthe reaction was quenched with water (3 mL)
4. concentrationThe crude mixture was concentrated in vacuo
5. additionAqueous NaOH (1 M, 150 mL) was added to the residue
6. extractionthe resulting mixture was extracted with Et2O (2×100 mL)
7. extractionthe resulting solution was extracted with Et2O (2×100 mL)
8. extractionThe combined organic layers from the acidic extraction
9. washwere washed with mixture of brine/1N HCl/sodium sulfite
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. dissolutionThe residue was dissolved in toluene (˜50 mL)
14. waitleft
15. waitto sit at rt for 3 days
16. filtrationA white solid was collected by vacuum filtration
17. customThe solid was dried under high vacuum

ORD-Eintrag

ord-f492e4589aad4f69a71b0cf2bdf560d4

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08349880B2