Diethyl Ether → 2-(Pyridin-3-ylmethyl)quinuclidin-3-amine

HRID 45282Notes

Reaction equation

HRID 45282 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH:8]2[C:13](=O)[CH:12]3[CH2:15][CH2:16][N:9]2[CH2:10][CH2:11]3)[CH:2]=1.CCOCC.C([O-])=O.[NH4+].C([BH3-])#[N:27].[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[NH2:27][CH:13]1[CH:12]2[CH2:15][CH2:16][N:9]([CH2:10][CH2:11]2)[CH:8]1[CH2:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 2723923Ammonium formateHCID 5003444Sodium cyanoborohydrideHCID 102200302-(Pyridin-3-ylmethyl)quinuclidin-3-one

Product 1

HCID 223113782-(Pyridin-3-ylmethyl)quinuclidin-3-amine

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of 2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-one (3.00 g, 13.9 mmol) in dry methanol (20 mL), under nitrogen, was added a 1 M solution of zinc chloride in ether (2.78 mL, 2.78 mmol). After stirring at ambient temperature for 30 min, this mixture was treated with solid ammonium formate (10.4 g, 167 mmol). After stirring another hour at ambient temperature, solid sodium cyanoborohydride (1.75 g, 27.8 mmol) was added in portions. The reaction was then stirred at ambient temperature overnight and terminated by addition of water (˜5 mL). The quenched reaction was partitioned between 5 M sodium hydroxide (10 mL) and chloroform (20 mL). The aqueous layer was extracted with chloroform (20 mL), and combined organic layers were dried (sodium sulfate), filtered and concentrated. This left 2.97 g of yellow gum. GCMS analysis indicated that the product was a 1:9 mixture of the cis and trans amines, along with a trace of the corresponding alcohol (98% total mass recovery).

Workup

  1. stirringAfter stirring another hour at ambient temperature
  2. stirringThe reaction was then stirred at ambient temperature overnight
  3. customterminated by addition of water (˜5 mL)
  4. customThe quenched reaction
  5. customwas partitioned between 5 M sodium hydroxide (10 mL) and chloroform (20 mL)
  6. extractionThe aqueous layer was extracted with chloroform (20 mL)
  7. dry with materialwere dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additiona 1:9 mixture of the cis and trans amines

Sources & evidence

ORD record
ord-8d963d294d9945c9a57f047fb513634f
Source dataset
uspto-grants-2013_09
Patent number
US08541446B2

Reaction notes

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