Ethanol → 7-Bromo-5-fluoro-1-benzofuran

2-Bromo-1-(2,2-diethoxy-ethoxy)-4-fluoro-benzene (60 g, 0.22 mol, Step A) was combined with Amberlyst-15 (20 g, Aldrich) in chlorobenzene (500 mL, Aldrich) and stirred with a paddle stirrer while the temperature was maintained at very gentle reflux. At the same time an azeotrope containing ethanol and chlorobenzene was removed via downward distillation. After 2 hours, more chlorobenzene was added (200 mL) and additional azeotrope was collected. The content of the flask was filtered and excess chlorobenzene was distilled (45° C., at ˜1 mm). The residue was purified by silica gel chromatography (5–10% ethyl ether/hexane) to give 7-bromo-5-fluoro-benzofuran (14 g, ˜33%) and taken to the next step. H1NMR (300 MHz, DMSOd6), ppm: 8.20 (d), 1H, 7.52 (m), 2H, 7.10 (d), 1H.

1. temperaturewas maintained at very gentle reflux
2. customwas removed via downward distillation
3. additionmore chlorobenzene was added (200 mL) and additional azeotrope
4. customwas collected
5. filtrationThe content of the flask was filtered
6. distillationexcess chlorobenzene was distilled (45° C., at ˜1 mm)
7. customThe residue was purified by silica gel chromatography (5–10% ethyl ether/hexane)

ORD record

ord-ed2b9230f1424e4abaa8bdd2be6c5379

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157455B2