Reacción #3386

Ecuación de reacción

HCl

tBuLi

2,3-dichloro-5-iodopyridine

1,2,3,5,6,7-hexahydropyrrolizinium perchlorate

→

oil

Rendimiento 54.3%

7a-(5,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizine

Rendimiento 54.3%

Disolventes

pentane

Et2O

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroprecooled to -100° C
2. 2
   workup.STIRRINGto stir for 20 minutes at -100° C.
3. 3
   Otrothe cold bath was removed
4. 4
   TemperaturaAfter warming to ambient temperature
5. 5
   workup.ADDITIONthe reaction mixture was poured over EtOAc
6. 6
   Otrothe phases were separated
7. 7
   Extracciónextracted with CH2Cl2 (2×)
8. 8
   Secadodried (MgSO4)
9. 9
   Concentraciónconcentrated
10. 10
    Otrothe residue was chromatographed (silica gel; CHCl3 /MeOH, 99.5:0.5)

Procedimiento

A solution of 1.7M tBuLi (4.7 mL, 8.0 mmol) in pentane was added to 2,3-dichloro-5-iodopyridine (from step 8a, 1.0 g, 3.65 mmol) in Et2O (15 mL) precooled to -100° C. After stirring for 2 minutes, 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (1.5 g, 7.3 mmol) was added, and the reaction mixture was allowed to stir for 20 minutes at -100° C. then gradually warm to -20° C. A solution of 2N HCl was added, and the cold bath was removed. After warming to ambient temperature, the reaction mixture was poured over EtOAc and the phases were separated. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 phases were combined, dried (MgSO4), concentrated and the residue was chromatographed (silica gel; CHCl3 /MeOH, 99.5:0.5) to afford a light yellow oil (510 mg, 54%). MS (CI/NH3) m/e: 257 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.59-1.71 (m, 2H), 1.80-2.08 (m, 6H), 2.64-2.72 (m, 2H), 3.11-3.20 (m, 2H), 7.99 (d, J=2.2 Hz, 1H), 8.36 (d, J=2.2 Hz, 1H).

Fuente