Tetrahydrofuran → 4-(3-bromophenyl)oxane-4-carbonitrile

Temperature

22.5 °C

3-Bromophenylacetonitrile (20.0 g, 102 mmole, 1 eq.), tetrahydrofuran (120 ml), 40% aqueous sodium hydroxide solution (180 ml, mmole, eq.), tetrabutylammonium hydrogensulfate (3.46 g, mmole, 0.1 eq.) were stirred in a reaction flask set for boiling at reflux. Thereafter, 2,2′-dichlorodiethylether (13.75 ml, 117.3 mmole, 0.1 eq.) was added with stirring at room temperature, 20-25° C. The resultant reaction mixture was boiled at reflux for 5-8 h at approximately 64° C. The reaction mixture was cooled to ambient temperature and ethyl acetate (154 ml) was added. The lower aqueous layer was separated and the organic layer evaporated down into a red oil. Iso-propanol (100 ml) and water (10 ml) were added to the oil and stirred at 0° C. overnight to yield a crystal slurry. The crystal slurry was vacuum filtered, washed with isopropanol (2×20 ml). The white crystalline solid was dried under vacuum at 40-45° C. Yield 18.57 g (68.4%): mp 82-85° C.; m/z 267 (m+1); 1H NMR (300 MHz, DMSO) δ7.75 (s, 1H), 7.6 (m, 2H), 7.44 (t, 1H), 4.02 (m, 2H), 3.66 (m, 2H), 2.14 (m, 4H).

1. temperatureat reflux
2. customThe resultant reaction mixture
3. temperatureat reflux for 5-8 h at approximately 64° C
4. temperatureThe reaction mixture was cooled to ambient temperature
5. customThe lower aqueous layer was separated
6. customthe organic layer evaporated down into a red oil
7. additionIso-propanol (100 ml) and water (10 ml) were added to the oil
8. stirringstirred at 0° C. overnight
9. customto yield a crystal slurry
10. filtrationfiltered
11. washwashed with isopropanol (2×20 ml)
12. customThe white crystalline solid was dried under vacuum at 40-45° C

ORD record

ord-a84e8c9e2ad846c88191bafd0bfce01b

Source dataset

uspto-grants-2002_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06346624B1