Pyridine → HCID 15430829, compound

Temperature

80 °C

An oven-dried 100 ml 3-necked round bottom flask was fitted with a thermometer, pressure equalised dropping funnel, magnetic stirrer and short path distillation set-up and the apparatus filled with nitrogen. Phosphorous oxychloride (9.09 g, 58.7 mmol) and pyridine (15.7 g) were charged to the flask and the mixture then cooled to −10° C. in an acetone/Drikold™ bath. A solution of 3-cyano-3-hydroxy-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octane in diethyl ether (45 ml, prepared in Step 1) was added dropwise to the reaction mixture keeping the temperature below 10° C. The mixture was then heated to 80° C. and the diethyl ether (about 40 ml) was distilled out. The condenser was re-arranged to reflux and the reaction was held at 80° C. for 24 hours after which it was cooled and stirred at ambient for 18 hours. The reaction mass was poured onto ice/water (50 ml) and sodium carbonate was added portionwise until the mixture was adjusted to pH8. The mixture was extracted with ethyl acetate (3×30 ml) and the combined extracts were washed with water(200 ml) and brine (200 ml). The extracts were dried (Na2SO4), filtered and concentration in vacuo to give 3-cyano-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]-oct-2-ene (1.16 g, 60% yield from 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-one; 73:27 exo:endo cyano).

1. customAn oven-dried 100 ml 3-necked round bottom flask was fitted with a thermometer, pressure
2. distillationshort path distillation set-up
3. additionthe apparatus filled with nitrogen
4. customthe temperature below 10° C
5. distillationthe diethyl ether (about 40 ml) was distilled out
6. temperatureto reflux
7. temperatureafter which it was cooled
8. additionThe reaction mass was poured onto ice/water (50 ml) and sodium carbonate
9. additionwas added portionwise until the mixture
10. extractionThe mixture was extracted with ethyl acetate (3×30 ml)
11. washthe combined extracts were washed with water(200 ml) and brine (200 ml)
12. dry with materialThe extracts were dried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentration in vacuo

ORD record

ord-870c8707d77d47c9ae8e629031066d71

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06323343B1