反応 #3421

反応方程式

n-BuLi

di-isopropylamine

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

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

→

title compound

収率 37.4%

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

収率 37.4%

溶媒

THF

反応条件

後処理

1. 1
   温度cooled to -78° C
2. 2
   温度The mixture was slowly warmed to room temperature
3. 3
   workup.STIRRINGstirred overnight
4. 4
   その他The reaction was quenched with 2N HCl
5. 5
   洗浄the mixture was washed with Et2O
6. 6
   抽出extracted with methylene chloride
7. 7
   その他dried
8. 8
   濃縮(MgSO4) and concentrated
9. 9
   その他The residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1)

実験手順

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)+.

出典