[CH2:1]([NH2:4])[CH:2]=[CH2:3].Cl.[CH2:6]([N:13]1[C@H:17]([CH2:18]Cl)[CH2:16][CH2:15][C@@H:14]1[CH2:20]Cl)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Na+].[I-].C([O-])(O)=O.[Na+]>C(#N)C>[CH2:6]([N:13]1[CH:17]2[CH2:16][CH2:15][CH:14]1[CH2:20][N:4]([CH2:1][CH:2]=[CH2:3])[CH2:18]2)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1Allylamine (9.5 mL, 0.13 mol) was added to a suspension of cis-1-benzyl-2,5-bis(chloromethyl)pyrrolidine hydrochloride (37.5 g, 0.13 mol, from step (e) above), NaI (47.6 g, 0.32 mol) and NaHCO3 (106.7 g, 1.27 mol) in acetonitrile (1.8 L). The reaction was heated at reflux for 8 h, filtered, and the filtrate concentrated in vacuo. The residue was partitioned between ethyl acetate and ice cold 1 N NaOH. The ethyl acetate layer was separated, dried (Na2SO4), filtered and concentrated in vacuo to afford 31.1 g of an oil. The oil was chromatographed on a column of silica (75 mm×220 mm) eluting with a mixture of chloroform, methanol and conc. NH4OH (240:9:1). Fractions (100 mL each) 5–10 were combined and concentrated in vacuo to afford 22.2 g (72%) of the sub-title compound.
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