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

Temperature

22.5 °C

3-Bromophenylacetonitrile (20.0 g, 102 mmole, 1 eq.), commercially available from Aldrich Chemical Co., Milwaukee, Wis., 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) δ 7.75 (s, 1 H), 7.6 (m, 2 H), 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-fbc3929f727747a88b7c569e48fe0bde

Source dataset

uspto-grants-2001_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06239285B1