3,5-Dibromopyridine → 7a-(5-bromo-3-pyridinyl)-hexahydro-1H-pyrrolizine

HRID 3313Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[Li]C(C)(C)C.Cl([O-])(=O)(=O)=O.[CH2:19]1[C:26]2[CH2:25][CH2:24][CH2:23][N+:22]=2[CH2:21][CH2:20]1>CCCCC>[Br:8][C:6]1[CH:7]=[C:2]([C:26]23[CH2:25][CH2:24][CH2:23][N:22]2[CH2:21][CH2:20][CH2:19]3)[CH:3]=[N:4][CH:5]=1

Participants

Conditions

Temperature: -95 °C

Procedure

3,5-dibromopyridine (500 mg, 2.11 mmol, Aldrich) was dissolved in Et2 O and cooled to -95° C. A solution of 2.5M t-BuLi (1.7M in pentane, 2.7 mL, 4.64 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (663 mg, 3.2 mmol) was added, and the reaction mixture was allowed to stir and warm to -10° C. and stir for 2 hours. The cold bath was removed, 2N HCl was added, and the phases were separated. The aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2 Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (160 mg, 28%): 1H NMR (CDCl3, 300 MHz) 67 1.57-1.71 (m, 2H), 1.79-2.04 (m, 6H), 2.62-2.73 (m, 2H), 3.11-3.20 (m, 2H), 8.04 (dd, J=2.0, 2.0 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.58 (d, J=2.0 Hz, 1H); MS (CI/NH3) m/z: 267/269 (M+H)+.

Workup

temperaturewarm to -10° C.
stirringstir for 2 hours
customThe cold bath was removed
addition2N HCl was added
customthe phases were separated
extractionextracted with CH2Cl2 (2×)
dry with materialdried (MgSO4)
concentrationconcentrated
customthe residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2)

Sources & evidence

ORD record: ord-d8f9af624c254aa681fb4cd3472eb869
Source dataset: uspto-grants-1998_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05733912

Reaction notes

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