7a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine → HCID 18934718, compound
Reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]23[CH2:15][CH2:14][CH2:13][N:12]2[CH2:11][CH2:10][CH2:9]3)=[CH:4][C:3]=1[CH3:16].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:16][C:3]1[CH:4]=[C:5]([C:8]23[CH2:15][CH2:14][CH2:13][N:12]2[CH2:11][CH2:10][CH2:9]3)[CH:6]=[N:7][CH:2]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
7a-(6-Chloro-5-methyl-3-pyridinyl)-hexahydro-1H-pyrrolizine (274 mg, 1.16 mmol, from Example 19c) and LAH (1.0M in THF, 1.2 mL, 1.16 mmol) were added to THF (4.5 mL), and the mixture was stirred at room temperature for 4 hours. An additional amount of LAH (1.0M in THF, 1.2 mL, 1.16 mmol) was added, and the reaction was stirred overnight. A further amount of LAH (2 equivalents) was added, and the reaction was stirred at room temperature for 24 hours and at 80° C. for 5 hours. The reaction was quenched with 10% K2CO3 solution, and the resulting slurry was filtered. The filtrate was diluted with EtOAc and 15% NaOH, and the phases were separated. The aqueous phase was extracted with methylene chloride, and all the organic solutions were combined, dried and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford the title compound as an oil (116 mg, 49%): 1H NMR (CDCl3, 300 MHz) δ1.57-1.71 (m, 2H), 1.77-2.06 (m, 6H), 2.32 (s, 3H), 2.66-2.74 (m, 2H), 3.12-3.19 (m, 2H), 7.63 (s, 1H), 8.24 (s, 1H), 8.50 (s, 1H); MS (CI/NH3) m/z: 203 (M+H)+.