Pyrrolizinium, 1,2,3,5,6,7-hexahydro-, perchlorate → 7a-(6-fluoro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine
Reaction equation
[F:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5](I)=[CH:4][N:3]=1.[Li]C(C)(C)C.Cl([O-])(=O)(=O)=O.[CH2:20]1[C:27]2[CH2:26][CH2:25][CH2:24][N+:23]=2[CH2:22][CH2:21]1>CCOCC.CCCCC>[F:1][C:2]1[N:3]=[CH:4][C:5]([C:27]23[CH2:26][CH2:25][CH2:24][N:23]2[CH2:22][CH2:21][CH2:20]3)=[CH:6][C:7]=1[CH3:8]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -95 °C
Procedure
2-Fluoro-5-iodo-3-methylpyridine (200 mg, 0.84 mmol) was dissolved in Et2O and cooled to -95° C. A solution of 2.5M t-BuLi (1.7M in pentane, 1.1 mL, 1.80 mmol) in pentane was added dropwise. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (265 mg, 1.26 mmol) was added, and the reaction mixture was allowed to warm to -10° C. with stirring 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 CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford the title compound as an oil (123 mg, 67%) 1H NMR (CDCl3, 300 MHz) δ1.55-1.71 (m, 2H), 1.78-2.04 (m, 6H), 2.26 (s, 3H), 2.64-2.72 (m, 2H), 3.11-3.18 (m, 2H), 7.70 (m, 1H), 8.09 (m, 1H); MS (CI/NH3) m/z: 221 (M+H)+.
Workup
- temperatureto warm to -10° C.
- 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, 99:1)
Sources & evidence
- ORD record
- ord-b6a3efbece064552a88a0a3c4985d4a0
- Source dataset
- uspto-grants-1998_03
- Patent number
- US05733912
Reaction notes
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