Reacción #741709

Ecuación de reacción

1-azabicyclo[3.2.1]oct-5-ylcarboxamide

vinylene carbonate

potassium carbonate

→

title compound

Rendimiento 16.0%

5-(1,3-Oxazol-2-yl)-1-azabicyclo[3.2.1]octane oxalate salt

Rendimiento 16.0%

Disolventes

—

polyphosphoric acid

ether

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas heated at 120°-130° C. for 2h
2. 2
   Temperaturato cool
3. 3
   workup.ADDITIONtreated with ice
4. 4
   Filtraciónthe mixture filtered
5. 5
   Otrothe organic layer separated
6. 6
   ExtracciónThe aqueous was again extracted with ether (2×80 ml) and all the ether
7. 7
   Secadodried (Na2SO4)
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   Otroto leave a yellow oil
10. 10
    OtroThis was chromatographed on a basic alumina column
11. 11
    Lavadoeluting with ethyl acetate
12. 12
    Otrothe material obtained
13. 13
    Otrorecrystallised from methanol/ether

Procedimiento

A stirred mixture of 1-azabicyclo[3.2.1]oct-5-ylcarboxamide (D20, 1.50 g, 0.0097 mole) and vinylene carbonate (1.2 g, 0.014 mole) in polyphosphoric acid (35 g) was heated at 120°-130° C. for 2h. The reaction mixture was allowed to cool, then treated with ice, before basifying with potassium carbonate solution. The aqueous was shaken well with ether, then the mixture filtered and the organic layer separated. The aqueous was again extracted with ether (2×80 ml) and all the ether extracts combined, dried (Na2SO4) and concentrated in vacuo to leave a yellow oil. This was chromatographed on a basic alumina column eluting with ethyl acetate and the material obtained converted to its oxalate salt and recrystallised from methanol/ether to give the title compound (E12) as a white solid (410 mg, 16%) m.p. 143°-145° C.

Fuente