Reaction #3386

Reaction equation

HCl

tBuLi

2,3-dichloro-5-iodopyridine

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

→

oil

Yield 54.3%

7a-(5,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizine

Yield 54.3%

Solvents

pentane

Et2O

Conditions

Workup

1. 1
   Otherprecooled to -100° C
2. 2
   workup.STIRRINGto stir for 20 minutes at -100° C.
3. 3
   Otherthe cold bath was removed
4. 4
   TemperatureAfter warming to ambient temperature
5. 5
   workup.ADDITIONthe reaction mixture was poured over EtOAc
6. 6
   Otherthe phases were separated
7. 7
   Extractionextracted with CH2Cl2 (2×)
8. 8
   Dryingdried (MgSO4)
9. 9
   Concentrationconcentrated
10. 10
    Otherthe residue was chromatographed (silica gel; CHCl3 /MeOH, 99.5:0.5)

Procedure

A solution of 1.7M tBuLi (4.7 mL, 8.0 mmol) in pentane was added to 2,3-dichloro-5-iodopyridine (from step 8a, 1.0 g, 3.65 mmol) in Et2O (15 mL) precooled to -100° C. After stirring for 2 minutes, 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (1.5 g, 7.3 mmol) was added, and the reaction mixture was allowed to stir for 20 minutes at -100° C. then gradually warm to -20° C. A solution of 2N HCl was added, and the cold bath was removed. After warming to ambient temperature, the reaction mixture was poured over EtOAc and the phases were separated. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 phases were combined, dried (MgSO4), concentrated and the residue was chromatographed (silica gel; CHCl3 /MeOH, 99.5:0.5) to afford a light yellow oil (510 mg, 54%). MS (CI/NH3) m/e: 257 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.59-1.71 (m, 2H), 1.80-2.08 (m, 6H), 2.64-2.72 (m, 2H), 3.11-3.20 (m, 2H), 7.99 (d, J=2.2 Hz, 1H), 8.36 (d, J=2.2 Hz, 1H).

Source