Bicarbonate Ion → HCID 22882072, compound

HRID 1458901Notes

Reaction equation

HRID 1458901 reaction equation
[CH2:1]([N:3]([CH2:15][CH3:16])[C:4]([CH:6]1[CH: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 22097565HCID 22097565, compound

Product 1

HCID 22882072HCID 22882072, compoundYield 40.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

(3R*, 4R*)-N,N-Diethyl-5oxo-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 (3.65L), 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. 3.5L 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-6-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 1.5L 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. custom3.5L 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-b140cfd0cd61447e84db9ef411a2066f
Source dataset
uspto-grants-1998_12
Patent number
US05852038

Reaction notes

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