Reacción #3421

Ecuación de reacción

n-BuLi

di-isopropylamine

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

1,2-dibromo-1,1,2,2-tetrafluoroethane

→

title compound

Rendimiento 37.4%

7a-(5-bromo-6-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine

Rendimiento 37.4%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooled to -78° C
2. 2
   TemperaturaThe mixture was slowly warmed to room temperature
3. 3
   workup.STIRRINGstirred overnight
4. 4
   OtroThe reaction was quenched with 2N HCl
5. 5
   Lavadothe mixture was washed with Et2O
6. 6
   Extracciónextracted with methylene chloride
7. 7
   Otrodried
8. 8
   Concentración(MgSO4) and concentrated
9. 9
   OtroThe residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1)

Procedimiento

n-BuLi (2.5M in hexanes, 0.252 mL, 0.63 mmol) was added to di-isopropylamine (0.082 mL, 0.63 mmol) in THF and stirred at room temperature for 10 minutes, then cooled to -78° C. 7a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (123 mg, 0.60 mmol, from Example 12d) and 1,2-dibromo-1,1,2,2-tetrafluoroethane (0.215 mL, 1.80 mmol) were added. The mixture was slowly warmed to room temperature and stirred overnight. The reaction was quenched with 2N HCl, and the mixture was washed with Et2O. The aqueous layer was basified with 15% NaOH and extracted with methylene chloride. The organic extracts were combined, dried, (MgSO4) and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford the title compound as an oil (64 mg, 37%). 1H NMR (CDCl3, 300 MHz) δ1.59-1.71 (m, 2H), 1.79-2.06 (m, 6H), 2.64-2.72 (m, 2H), 3.12-3.19 (m, 2H), 8.14 (dd, J=8.8, 2.2 Hz, 1H), 8.19 (dd, J=2.2, 1.2 Hz, 1H); MS (CI/NH3) m/z: 285/287 (M+H)+.

Fuente