Réaction #3391

Équation de réaction

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

nBuLi

diisopropylamine

HCl

2,6-dichloropyridine

→

oil

Rendement 17.2%

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

Rendement 17.2%

Solvants

EtOAc

—

hexanes

THF

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 1 hour at -78° C
3. 3
   workup.STIRRINGto stir for 2 hours at -78° C.
4. 4
   Températurethen warm to ambient temperature
5. 5
   AutreThe phases were separated
6. 6
   Extractionextracted with CH2Cl2 (2×)
7. 7
   Séchagedried (MgSO4)
8. 8
   Concentrationconcentrated
9. 9
   Autrethe residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2)

Mode opératoire

A solution of 2.5M nBuLi (675 μL, 1.7 mmol) in hexanes was added to diisopropylamine (220 μL, 1.7 mmol) in THF (4.5 mL) at ambient temperature. After 10 minutes of stirring, the reaction mixture was cooled to -78° C., 2,6-dichloropyridine (237 μL, 1.60 mmol) was added neat, and stirring was continued for 1 hour at -78° C. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (500 mg, 2.40 mmol) was added, and the reaction mixture was allowed to stir for 2 hours at -78° C. then warm to ambient temperature. A solution of 2N HCl was added, and the mixture was then poured over EtOAc. The phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (70.6 mg, 17%). MS (CI/NH3) m/e: 257/259 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.47-1.61 (m, 2H), 1.77-1.90 (m, 2H), 2.10-2.25 (m, 4H), 2.67-2.75 (m, 2H), 3.03-3.11 (m, 2H), 7.19 (d, J=8.5 Hz, 1H), 8.37 (d, J=8.5 Hz, 1H).

Source