Sodium Carbonate → HCID 18352161, compound

Participants

Reaction Conditions

Reaction Steps

An oven-dried 50 ml 3-necked round bottom flask was fitted with a reflux condenser, thermometer and magnetic stirrer and an atmosphere of nitrogen was introduced. Phosphorous oxychloride (1.9 ml, 3.16 g, 24 mmol) and pyridine (14.7 ml) were charged and the mixture then cooled to −10° C. in an acetone/Drikold™ bath. 3-Cyano-3-hydroxy-8-(2,2-difluoroethyl)-8-azabicyclo[3.2.1]octane (2 g, assumed 9 mmol, from Step 2) was added in one portion and the resulting exotherm raised the reaction mass temperature to 55° C. The mixture was then heated to 80° C. and held at this temperature for 24 hours. The reaction mass was cooled to ambient, then added to a stirred mixture of ice/water (100 ml). The drowned out mass was made basic by addition of solid sodium carbonate (6 g) and the resulting aquesous solution was then extracted with ethyl acetate (3×100 ml). The combined organics were washed with brine (100 ml), dried (Na2SO4) and concentrated in vacuo to give 3-cyano-8-(2,2-difluoroethyl)-8-azabicyclo[3.2.1]oct-2-ene as a brown oil (0.41 g, 13% yield).

Provenance & Evidence