Benzaldehyde → 3-(Benzylamino)quinuclidine

HRID 349215

Reaction equation

HRID 349215 reaction equation
Cl.Cl.[NH2:3][CH:4]1[CH:9]2[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]2)[CH2:5]1.C([O-])([O-])=O.[Na+].[Na+].[CH:18](=O)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[BH4-].[Na+]>CCO>[C:19]1([CH2:18][NH:3][CH:4]2[CH:9]3[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]3)[CH2:5]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 10340Sodium CarbonateHCID 197853Quinuclidine, 3-amino-, dihydrochlorideHCID 4311764Sodium borohydride

Product 1

HCID 2615513-(Benzylamino)quinuclidineYield 76%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3-aminoquinuclidine dihydrochloride (8.0 g, 40.0 mmol) in EtOH (100 mL) was added excess Na2CO3 and the mixture was stirred for 1 h and then filtered. To this solution was added benzaidehyde (3.2 g, 30.0 mmol) and the reaction was stirred at room temperature for 2 h and then NaBH4 (3 pellets, 0.4 g ea.) was added and the reaction was stirred overnight at room temperature. The solvent was evaporated in vacuo and the residue was partitioned between 10% Na2CO3 and EtOAc. The organic layer was separated, dried over K2CO3, filtered and the solvent was evaporated in vacuo. The residue was chromatographed on silica (92/8 CHCl3/1.0 M NH3 in MeOH) to give N-phenylmethyl-1-azabicyclo[2.2.2]octan-3-amine (4.2 g, 76%) as an intermediate, a pale yellow oil. MH+=217. 1H NMR (CDCl3) 1.4 (m, 3H), 1.7 (m, 1H), 1.9 (m, 2H), 2.45 (2m, 1H), 2.8 (m, 5H), 3.2 (m, 1H), 3.75 (d, 2H), 7.3 (m, 5H).

Workup

  1. filtrationfiltered
  2. stirringthe reaction was stirred at room temperature for 2 h
  3. stirringthe reaction was stirred overnight at room temperature
  4. customThe solvent was evaporated in vacuo
  5. customthe residue was partitioned between 10% Na2CO3 and EtOAc
  6. customThe organic layer was separated
  7. dry with materialdried over K2CO3
  8. filtrationfiltered
  9. customthe solvent was evaporated in vacuo
  10. customThe residue was chromatographed on silica (92/8 CHCl3/1.0 M NH3 in MeOH)

Sources & evidence

ORD record
ord-480e3d3718e64d739c9c618bf7b020c4
Source dataset
uspto-grants-2007_02
Patent number
US07179818B2

Linked notes

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