Pyridine → 2-(5-Bromo-7-chlorobenzofuran-2-yl)ethanol

Temperature

70 °C

The product of step A (14.0 g, 42.76 mmol) was added to a mixture of but-3-yn-1-ol (3.24 mL, 42.79 mmol), copper(II)oxide (3.67 g, 25.67 mmol), pyridine (21.3 mL) and N-methylpyrrolidone (85.0 mL). The reaction mixture was heated to 70° C. for 12 h then 100° C. for a further 2.5 h. The mixture was diluted with MTBE (200 mL), washed successively with 5% aq NH4OH (200 mL), 0.5 M NaOH (200 mL) and saturated brine solution (200 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to give the crude product which was purified by column chromatography (SiO2, 4:1 hexanes/ethyl acetate) providing 2-(5-bromo-7-chlorobenzofuran-2-yl)ethanol (7.8 g, 66%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 7.52 (d, J=1.6 Hz, 1H), 7.37 (d, J=2.0 Hz, 1H), 6.52-6.51 (m, 1H), 4.02 (q, J=6.0 Hz, 2H), 3.09 (t, J=6.2 Hz, 2H), 1.65 (t, J=5.6 Hz, 1H).

1. washwashed successively with 5% aq NH4OH (200 mL), 0.5 M NaOH (200 mL) and saturated brine solution (200 mL)
2. extractionextracted with ethyl acetate (3×75 mL)
3. dry with materialThe combined organic extracts were dried over Na2SO4
4. concentrationconcentrated in vacuo
5. customto give the crude product which
6. customwas purified by column chromatography (SiO2, 4:1 hexanes/ethyl acetate)

ORD record

ord-73d72715cbfb424e82ac07ee404f51b7

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067949B2