تفاعل #3421

معادلة التفاعل

n-BuLi

di-isopropylamine

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

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

→

title compound

المردود 37.4%

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

المردود 37.4%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooled to -78° C
2. 2
   درجة الحرارةThe mixture was slowly warmed to room temperature
3. 3
   workup.STIRRINGstirred overnight
4. 4
   أخرىThe reaction was quenched with 2N HCl
5. 5
   غسيلthe mixture was washed with Et2O
6. 6
   استخلاصextracted with methylene chloride
7. 7
   أخرىdried
8. 8
   تركيز(MgSO4) and concentrated
9. 9
   أخرىThe residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1)

الإجراء التجريبي

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)+.

المصدر