Sodium Iodide → 3-Allyl-8-benzyl-3,8-diazabicyclo[3.2.1]octane

HRID 1743695Notes

Reaction equation

HRID 1743695 reaction equation
[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]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 7853AllylamineHCID 516892Sodium BicarbonateHCID 22940372Cis-1-benzyl-2,5-bis(chloromethyl)pyrrolidine hydrochloride

Product 1

HCID 222355893-Allyl-8-benzyl-3,8-diazabicyclo[3.2.1]octaneYield 98.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Allylamine (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.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 8 h
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe residue was partitioned between ethyl acetate and ice cold 1 N NaOH
  6. customThe ethyl acetate layer was separated
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-03e0cefb5d4c4905bea7fec2d9619c0b
Source dataset
uspto-grants-2006_03
Patent number
US07012074B2

Reaction notes

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