Reacción #3394

Ecuación de reacción

2-Fluoro-5-iodopyridine

t-BuLi

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

→

oil

Rendimiento 40.4%

7a-(6-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine

Rendimiento 40.4%

Disolventes

Et2O

pentane

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGto stir for 10 minutes at -78° C.
2. 2
   Temperaturato warm to -20° C
3. 3
   OtroThe cold bath was removed
4. 4
   workup.ADDITION2N HCl was added
5. 5
   Extracciónthe mixture was extracted with Et2O
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, 98:2)

Procedimiento

2-Fluoro-5-iodopyridine (200 μL, 0.90 mmol) was dissolved in Et2O and cooled to -78° C. A solution of 2.5M t-BuLi (1.2 mL, 1.98 mmol) in pentane was added, and the reaction was stirred for 2 minutes. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (375 mg, 1.80 mmol) was added, and the reaction mixture was allowed to stir for 10 minutes at -78° C. then allowed to warm to -20° C. The cold bath was removed, 2N HCl was added, and the mixture was extracted with Et2O. The phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2 Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (75 mg, 40%). 1H NMR (CDCl3, 300 MHz) δ1.58-1.73 (m, 2H), 1.79-2.05 (m, 6H), 2.64-2.73 (m, 2H), 3.12-3.19 (m, 2H), 6.82 (dd, J=8.4, 2.7 Hz, 1H), 7.90 (m, 1H), 8.30 (dd, J=1.4, 0.7 Hz, 1H); MS (CI/NH3) m/z: 207 (M+H)+.

Fuente