1,2-Dimethoxyethane → 1-Azabicyclo(2.2.2)octane-3-carbonitrile

HRID 588335

Reaction equation

HRID 588335 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C:3](=O)[CH2:2]2.C1(C)C=CC(S([CH2:19][N+:20]#[C-])(=O)=O)=CC=1.COCCOC.CC(C)([O-])C.[K+]>C(O)C>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([C:19]#[N:20])[CH2:2]2

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 195073-QuinuclidinoneHCID 161915Tosylmethyl isocyanideHCID 23665647Potassium tert-butoxide

Product 1

HCID 1428651-Azabicyclo(2.2.2)octane-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

20.4 g (163 mmol) of 3-quinuclidinone and 41.4 g (212 mmol) of (4-toluenesulfonyl)methyl isocyanide are introduced into 435 ml of 1,2-dimethoxyethane and 16 ml of dry ethanol while cooling in ice. 45.7 g (407 mmol) of potassium tert-butoxide are slowly added in such a way that the temperature does not rise above 10° C. The mixture is then heated at 40° C. for 2.5 h. After cooling to RT, the resulting solid is filtered off. The filtrate is concentrated and chromatographed on neutral alumina (mobile phase: dichloromethane→ethyl acetate→ethyl acetate/methanol 50:1). 22.9 g (quant.) of the racemic product are obtained in slightly impure form.

Workup

  1. temperaturewhile cooling in ice
  2. customdoes not rise above 10° C
  3. temperatureAfter cooling to RT
  4. filtrationthe resulting solid is filtered off
  5. concentrationThe filtrate is concentrated
  6. customchromatographed on neutral alumina (mobile phase: dichloromethane→ethyl acetate→ethyl acetate/methanol 50:1)
  7. custom22.9 g (quant.) of the racemic product are obtained in slightly impure form

Sources & evidence

ORD record
ord-0c15cf9fcccf45428de45158e4dc2c28
Source dataset
uspto-grants-2016_01
Patent number
US09227964B2

Linked notes

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