Uses
4''-Hydroxy-3''-iodobiphenyl-4-carbonitrile is the major component of the byproduct in the synthesis of 4''-Hydroxy-3'',5''-diiodo-[1,1''-biphenyl]-4-carbonitrile (H005080), which is a useful building block compound, and has been used in the preparation of plasminogen activator inhibitor antagonists.
Synthesis
4'-Hydroxy-4'-cyanobiphenyl (6.00 g, 30.8 mmol) was used as a raw material, which was dissolved in methanol (90 mL) at 0 °C, and sodium iodide (4.61 g, 30.8 mmol) and sodium hydroxide (1.23 g, 30.8 mmol) were added sequentially. Subsequently, aqueous sodium hypochlorite (47 mL, 5.25% Clorox, 2.29 g, 30.8 mmol) was slowly added at 45 °C. The reaction mixture was stirred at 0 °C for 1 h and then gradually warmed up to room temperature. The reaction mixture was diluted with sodium thiosulfate solution (10 mL) and water (80 mL) and the pH was adjusted to 7 by addition of sodium dihydrogen phosphate. the mixture was extracted with dichloromethane (2 x 90 mL), the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a white powder. The crude product was crystallized by dichloroethane/hexane and purified by chromatography on a silica gel column with dichloromethane to give 4'-hydroxy-3'-iodobiphenyl-4-carbonitrile (5.19 g, 53% yield). Mass spectrum (DCI) m/z 339 [M + NH4]+.
References
[1] Organic Process Research and Development, 2005, vol. 9, # 1, p. 45 - 50
[2] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 3, p. 689 - 693
[3] Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 38 - 55
[4] Patent: US2003/153548, 2003, A1
[5] Patent: US2003/134835, 2003, A1
