反応 #3389

反応方程式

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

nBuLi

diisopropylamine

2,6-difluoropyridine

→

oil

収率 50.2%

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

収率 50.2%

溶媒

—

hexanes

THF

反応条件

後処理

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 1 hour at -78° C
3. 3
   その他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
   その他the phases were separated
7. 7
   抽出extracted with CH2Cl2 (2×)
8. 8
   乾燥dried (MgSO4)
9. 9
   濃縮concentrated
10. 10
    その他chromatographed (silica gel; CHCl3 /MeOH, 98:2)

実験手順

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).

出典