Phosphorus oxychloride → 4-Isocyano-1,2,3,6-tetrahydro-1,1'-biphenyl

Potassium tert-butoxide (34.3 g, 306 mmol) was added portionwise to a solution of 4-phenyl-1-formamidocyclohexene (13.6 g, 68 mmol) (Biiorg. Med. Chem; 8; 6; 2000; 1343) in tert-butanol (150 ml), and the mixture stirred for 2 hours, with sufficient heating to ensure solution. Phosphorous oxychloride (7.82 g, 51 mmol) was added dropwise, with cooling of the reaction vessel, and once additon was complete, the reaction was stirred at room temperature for 24 hours. TLC analysis showed starting material remaining, so additional potassium tert-butoxide (3.8 g, 34 mmol) and phosphorous oxychloride (1.57 ml, 17 mmol) were added, and the reaction stirred for a further 45 minutes. The mixture was concentrated under reduced pressure, the residue poured into brine (500 ml) and extracted with dichloromethane (100 ml, 3×50 ml). The combined organic solutions were washed with water (100 ml), brine (200 ml), dried (Na2SO4) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using hexane:ethyl acetate (90:10) as eluant to afford the title compound, 5.8 g.

1. temperaturewith sufficient heating
2. temperaturewith cooling of the reaction vessel, and once additon
3. stirringthe reaction was stirred at room temperature for 24 hours
4. stirringthe reaction stirred for a further 45 minutes
5. concentrationThe mixture was concentrated under reduced pressure
6. additionthe residue poured into brine (500 ml)
7. extractionextracted with dichloromethane (100 ml, 3×50 ml)
8. washThe combined organic solutions were washed with water (100 ml), brine (200 ml)
9. dry with materialdried (Na2SO4)
10. customevaporated under reduced pressure
11. customThe crude product was purified by column chromatography on silica gel

ORD record

ord-e45248bc0e65485f8c0750d848aa4d0f

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06914160B1