反应 #3389

反应方程式

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

nBuLi

diisopropylamine

2,6-difluoropyridine

→

oil

收率 50.2%

7a-(2,6-difluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine

收率 50.2%

溶剂

—

hexanes

THF

反应条件

后处理

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 1 hour at -78° C
3. 3
   其他the cold bath was removed
4. 4
   温度After warming to ambient temperature
5. 5
   workup.ADDITIONa solution of 2N HCl was added
6. 6
   其他the phases were separated
7. 7
   萃取extracted with CH2Cl2 (2×)
8. 8
   干燥dried (MgSO4)
9. 9
   浓缩concentrated
10. 10
    其他chromatographed (silica gel; CHCl3 /MeOH, 98:2)

实验过程

A solution of 2.5M nBuLi (675 μL, 1.7 mmol) in hexanes was added to diisopropylamine (220 μL, 1.6 mmol) in THF (4.5 mL) at ambient temperature. After 10 minutes of stirring, the reaction mixture was cooled to -78° C., 2,6-difluoropyridine (145 μL, 1.6 mmol) was introduced, and stirring was continued for 1 hour at -78° C. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (500 mg, 2.4 mmol) was then added, and the cold bath was removed. After warming to ambient temperature, a solution of 2N HCl was added and the phases were separated after pouting the reaction mixture over EtOAc. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 extracts were combined, dried (MgSO4), concentrated and chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (180 mg, 50%). MS (CI/NH3) m/e: 225 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.5-1.63 (m, 2H), 1.78-1.89 (m, 2H), 1.92-2.10 (m, 4H), 2.63-2.70 (m, 2H), 3.08-3.12 (m, 2H), 6.72 (dd, J=8.1, 3.0 Hz, 1H), 8.33 (dd, J=18.0, 8.1 Hz, 1H).

来源