Sodium Carbonate → HCID 15430829, compound

Participants

Reaction Conditions

Reaction Steps

A dry 25 ml 3-necked round bottom flask was fitted with a reflux condenser, thermometer and magnetic stirrer and the apparatus was filled with a nitrogen atmosphere. Phosphorous oxychloride (1.34, 8.7 mmol) and pyridine (6.22 g) were charged to the flask and the mixture then cooled to −10° C. in an acetone/Drikold™ bath. 3-Cyano-3-hydroxy-8-(2,2,2-trifluoroethyl)-8-azabicycio[3.2.1]octane (0.92 g, 3.9 mmol—assumed, prepared in Step 1) was added in one portion and the resultant exotherm raised the reaction mass temperature to 12° C. The mixture was heated to 80° C. and held at this temperature for 23 hours after which the mixture was cooled to ambient. The reaction mixture was poured onto ice/water (50 ml) and sodium carbonate added portionwise until the mixture was adjusted to pH8. The resulting mixture was extracted with ethyl acetate (3×30 ml), the combined extracts were dried (Na2SO4), filtered and concentrated in vacuo to give 3-cyano-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]oct-2-ene (0.8 g, 72% yield from 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]-octan-3-one; 74:26 exo:endo cyano).

Provenance & Evidence