Sodium Carbonate → HCID 15430829, compound

Participants

Reaction Conditions

Reaction Steps

An oven-dried 25 ml 3-necked round bottom flask was fitted with a reflux condenser, thermometer and magnetic stirrer and the apparatus filled with nitrogen. Phosphorous oxychloride (1.41 g, 9.1 mmol) and pyridine (6.53 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-azabicyclo[3.2.1]octane (0.97 g, 4.1 mmol—assumed, prepared in Step 1) was added in one portion and the resultant exotherm raised the reaction mass temperature to 20° C. The mixture was then heated to 80° C. and held at this temperature for 24 hours, after which the reaction mixture was cooled and stirred at ambient for 18 hours. The reaction mass was poured onto ice/water (50 ml) and solid sodium carbonate was added portionwise until the mixture was adjusted to pH8. The 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 (0.51 g, 51% yield from 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-one; 60:40 exo:endo cyano).

Provenance & Evidence