Sodium Hydroxide → (2S,3E)-4-Bromo-1-(4-fluorophenoxy)but-3-en-2-ol

Temperature

0 °C

AlCl3 (2.79 g, 21 mmol) was added in portions to a mixture of lithium aluminum hydride (LAH) (1.06 g, 28 mmol) and ether (70 mL). A solution of (3S)-1-bromo-4-(4-fluorophenoxy)-3-hydroxy-1-butyne (14 mmol) in ether (10 mL) was added cautiously. A vigorous reaction with evolution of gas was observed. The mixture was warmed to reflux on a water bath for 30 minutes. The reaction mixture was then cooled to 0° C. and treated with 2.8 mL water (slowly, vigorous reaction), 2.8 mL 15% NaOH, and finally 8.4 mL water. The resulting suspension was then stirred 10 minutes, filtered and the solids were washed with THF and ether. The solution was concentrated under vacuum to afford 2.94 g (81% yield for two steps) of (1E,3S)-1-bromo-4-(4-fluorophenoxy)-3-hydroxy-1-butene, a compound of formula (DD); 1H NMR (CDCl3) δ 2.41 (t, 1H), 3.85 (dd, 1H), 3.99 (dd, 1H), 4.50 (m, 1H), 6.31 (dd, 1H), 6.52 (dd, 1H), 6.83 (m, 2H), 6.97 (t, 2H) ppm.

1. customA vigorous reaction with evolution of gas
2. temperatureThe mixture was warmed
3. temperatureto reflux on a water bath for 30 minutes
4. filtrationfiltered
5. washthe solids were washed with THF and ether
6. concentrationThe solution was concentrated under vacuum

ORD record

ord-4b9c1a8f21384ff5abef936e5e4e0889

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928255B2