Bicarbonate Ion → HCID 22882072, compound

HRID 862133Notes

Reaction equation

HRID 862133 reaction equation
[CH2:1]([N:3]([CH2:15][CH3:16])[C:4]([C@@H:6]1[C@H:11]2[CH2:12][CH2:13][N:8]([CH2:9][C:10]2=[O:14])[CH2:7]1)=[O:5])[CH3:2].C([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.C(=O)(O)[O-]>C(O)C>[CH2:15]([N:3]([CH2:1][CH3:2])[C:4]([C@H:6]1[C@@H:11]2[CH2:12][CH2:13][N:8]([CH2:9][C:10]2=[O:14])[CH2:7]1)=[O:5])[CH3:16]

Participants

5

Reactant 3

HCID 769Bicarbonate IonHCID 12362976dibenzoyl-L(+)tartaric acidHCID 22882067HCID 22882067, compound

Product 1

HCID 22882072HCID 22882072, compoundYield 40.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

(3R*,4R*)-N,N-Diethyl-5-oxo-1-azabicyclo[2.2.2]octane-3-carboxamide (180 g, 0.804 mol) and (-)-dibenzoyl-L-tartaric acid (L-DBT) monohydrate (211 g, 0.561 mol) were added to ethanol (3.65 L), and the resultant mixture was heated at reflux until a clear solution was obtained. The solution was rapidly cooled down to c.a. 40° C. in a water-bath, and allowed to stand overnight to form crystals, which were collected by filtration. The obtained crystals (100.5 g, 21.5%) were found to be (+)-(3R,4R)-N,N-diethyl-5-oxo-1-azabicyclo[2.2.2]-octane-3-carboxamide L-DBT salt with 97% optical purity. An additional amount of (-)-L-DBT monohydrate (90.6 g, 0.241 mol) was added to the mother liquor, which was concentrated to c.a. 3.5 L by evaporation. The resulting mixture was heated at reflux to give a clear solution, which was allowed to stand at room temperature. After 2 days, formed crystals were collected by filtration. The crystals (117 g, 25%) were found to be (-)-(3S,4S)-N,N-diethyl-5-oxo-1-azabicyclo[2.2.2]-octane-3-carboxamide L-DBT salt with 92% optical purity. The same resolution process was repeated starting from 220 g of (3R*,4R*)-N,N-diethyl-5-oxo-1-azabicyclo[2.2.2]-octane-3-carboxamide. From this run, the L-DBT salt of the (+) enantiomer (180 g, 31%) with 95% optical purity and the L-DBT salt of the (-) enantiomer (91 g, 16%) with 97% optical purity were obtained. The L-DBT salt of the (-) enantiomer from the above two runs were combined, and suspended in 1.5 l of ethanol. The resulting suspension was heated at reflux for 3 hours, and allowed to stand overnight at room temperature. The obtained crystals were converted to the free amine by base treatment (aqueous bicarbonate) followed by extraction with methylene chloride to afford (-)-(3S,4S)-N,N-diethyl-5-oxo-1-azabicyclo[2.2.2]-octane-3-carboxamide (73 g, 18%) having greater than 99% optical purity. Similarly, 83 g of of the (+) enantiomer (21%) was obtained with greater than 99% optical purity. The above mentioned optical purities were determined using a chiral HPLC. The absolute configuration was determined by X-ray crystallography of the dibenzoyl-L-tartaric acid salt of the (-) enantiomer.

Workup

  1. temperatureat reflux until a clear solution
  2. customwas obtained
  3. temperatureThe solution was rapidly cooled down to c.a
  4. custom40° C. in a water-bath, and allowed
  5. customto form crystals, which
  6. filtrationwere collected by filtration
  7. concentrationwas concentrated to c.a
  8. custom3.5 L by evaporation
  9. temperatureThe resulting mixture was heated
  10. temperatureat reflux
  11. customto give a clear solution, which
  12. customto stand at room temperature
  13. waitAfter 2 days
  14. customformed crystals
  15. filtrationwere collected by filtration
  16. customFrom this run, the L-DBT salt of the (+) enantiomer (180 g, 31%) with 95% optical purity and the L-DBT salt of the (-) enantiomer (91 g, 16%) with 97% optical purity were obtained
  17. temperatureThe resulting suspension was heated
  18. temperatureat reflux for 3 hours
  19. waitto stand overnight at room temperature
  20. extractionfollowed by extraction with methylene chloride

Sources & evidence

ORD record
ord-3db1179783364fe9928bf07569fd58c5
Source dataset
uspto-grants-1998_02
Patent number
US05716965

Reaction notes

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