Water → (2S)-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-one

HRID 82427Notes

Reaction equation

HRID 82427 reaction equation
O.C(=O)(O)[O-].[Na+].C1(C)C=CC(C([C@](C(O)=O)(O)[C@](C(C2C=CC(C)=CC=2)=O)(O)C(O)=O)=O)=CC=1.[N:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][C@H:42]2[C:47](=[O:48])[CH:46]3[CH2:49][CH2:50][N:43]2[CH2:44][CH2:45]3)[CH:36]=1>ClCCl>[N:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][C@H:42]2[C:47](=[O:48])[CH:46]3[CH2:45][CH2:44][N:43]2[CH2:50][CH2:49]3)[CH:36]=1

Participants

5

Reactant 3

HCID 962WaterHCID 516892Sodium BicarbonateHCID 131729021HCID 131729021, compound

Product 1

HCID 66669607(2S)-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-oneYield 96.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Water (46.25 L) and sodium bicarbonate (4.35 kg, 51.8 mol) were added to a 200 L flask. Upon complete dissolution, dichloromethane (69.4 L) was added. (2S)-2-((3-Pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-one di-p-toluoyl-D-tartrate salt (11.56 kg, 19.19 mol) was added, and the reaction mixture was stirred for between 2 min and 10 min. The layers were allowed to separate for a minimum of 2 min (additional water (20 L) was added when necessary to partition the layers). The organic phase was removed and dried over anhydrous sodium sulfate. Dichloromethane (34.7 L) was added to the remaining aqueous phase, and the suspension was stirred for between 2 min and 10 min. The layers were allowed to separate for between 2 min and 10 min. Again, the organic phase was removed and dried over anhydrous sodium sulfate. The extraction of the aqueous phase with dichloromethane (34.7 L) was repeated one more time, as above. Samples of each extraction were submitted for chiral HPLC analysis. The sodium sulfate was removed by filtration, and the filtrates were concentrated to obtain (2S)-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-one (4.0 kg) as a solid.

Workup

  1. additionwas added
  2. customto separate for a minimum of 2 min (additional water (20 L)
  3. additionwas added when necessary
  4. customto partition the layers)
  5. customThe organic phase was removed
  6. dry with materialdried over anhydrous sodium sulfate
  7. additionDichloromethane (34.7 L) was added to the remaining aqueous phase
  8. stirringthe suspension was stirred for between 2 min and 10 min
  9. customto separate for between 2 min and 10 min
  10. customAgain, the organic phase was removed
  11. dry with materialdried over anhydrous sodium sulfate
  12. extractionThe extraction of the aqueous phase with dichloromethane (34.7 L)
  13. extractionSamples of each extraction
  14. customThe sodium sulfate was removed by filtration
  15. concentrationthe filtrates were concentrated

Sources & evidence

ORD record
ord-ef908063fb0541b6a6703aff57e7d1c5
Source dataset
uspto-grants-2014_09
Patent number
US08846715B2

Reaction notes

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