Sodium Carbonate → HCID 18352161, compound

Temperature

55 °C

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).

1. customAn oven-dried 50 ml 3-necked round bottom flask was fitted with a reflux condenser
2. additionthermometer and magnetic stirrer and an atmosphere of nitrogen was introduced
3. temperatureThe mixture was then heated to 80° C.
4. temperatureThe reaction mass was cooled to ambient,
5. extractionthe resulting aquesous solution was then extracted with ethyl acetate (3×100 ml)
6. washThe combined organics were washed with brine (100 ml)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated in vacuo

ORD record

ord-f65544c068674ee7ba5f1542f168fd99

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06323343B1