Triethylamine → N-[(3-chlorophenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine

HRID 349216

Reaction equation

HRID 349216 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.CCN(CC)CC.[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH:23]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1.[OH-].[Na+].O>[Cl:19][C:20]1[CH:21]=[C:22]([CH2:23][NH:3][CH:4]2[CH:9]3[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]3)[CH2:5]2)[CH:25]=[CH:26][CH:27]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 114773-ChlorobenzaldehydeHCID 197853Quinuclidine, 3-amino-, dihydrochlorideHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 17158964N-[(3-chlorophenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amineYield 30%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of of 3-aminoquinuclidine dihydrochloride (2.0 g, 10.0 mmol), NEt3 (1.3 mL) and 3-chlorobenzaldehyde (1.5 g, 11.0 mmol) in THF (50 mL) was stirred at room temperature. To this was added Na(OAc)3BH 13.2 g, 15 mmol) and the reaction was stirred overnight. The reaction mixture was diluted with 3N NaOH and water and extracted with EtOAc. The organic extracts were combined, washed with water and then brine and dried over K2CO3. The solution was filtered and the solvent was evaporated in vacuo to give an oil which was chromatographed on silica (94/6 CHCl3/0.5 M NH3 in MeOH). The appropriate fractions were combined and the solvent was evaporated in vacuo to give N-[(3-chlorophenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine (0.75 g, 30%) as an intermediate, a light yellow semi-solid. MH+=251,253. The 1H NMR was consistent with the assigned structure.

Workup

  1. stirringwas stirred overnight
  2. extractionextracted with EtOAc
  3. washwashed with water
  4. dry with materialbrine and dried over K2CO3
  5. filtrationThe solution was filtered
  6. customthe solvent was evaporated in vacuo
  7. customto give an oil which
  8. customwas chromatographed on silica (94/6 CHCl3/0.5 M NH3 in MeOH)
  9. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-91f1822674c442d28b532453a12610e5
Source dataset
uspto-grants-2007_02
Patent number
US07179818B2

Linked notes

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