3-Quinuclidinone → HCID 23313737, compound

HRID 745547Notes

Reaction equation

HRID 745547 reaction equation
[Mg].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10]Br)=[CH:5][CH:4]=1.[N:12]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[C:14](=[O:20])[CH2:13]2>O1CCCC1>[ClH:2].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:14]2([OH:20])[CH:15]3[CH2:18][CH2:19][N:12]([CH2:17][CH2:16]3)[CH2:13]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 195073-QuinuclidinoneHCID 230291-(2-Bromoethyl)-4-chlorobenzeneHCID 5462224Magnesium2×

Product 1

HCID 23313737HCID 23313737, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 2.43 g (0.10 mole) of magnesium in 30 ml of anhydrous tetrahydrofuran under an N2 atmosphere is added slowly 21.95 g (0.10 mole) of 2-(4-chlorophenyl)ethyl bromide. The addition rate is such that a gentle reflux of the solvent is maintained. After the addition is complete the mixture is refluxed until the magnesium metal is thoroughly reacted. Cool the reaction mixture to 40°-45° C. and add a solution of 12.52 g (0.1 mole) of 3-quinuclidinone in 100 ml of anhydrous tetrahydrofuran at a sufficient rate to bring the mixture to a gentle reflux. When the addition is complete reflux the mixture for 1 hour. Follow the progress of the reaction by thin-layer chromatography on silica gel (acetonitrile: ammonium hydroxide, 95:5). At the completion of the reaction cool the mixture to 0°-5° C. in an ice/water bath. Quench the reaction mixture by the slow addition of 20 ml of 10% hydrochloric acid solution. Remove the tetrahydrofuran in vacuo. Add 100 ml of water to the residue then add sufficient 10% sodium hydroxide with cooling to bring the pH of the mixture to 11-12. Remove any magnesium hydroxide which may have precipitated by filtration, then wash the filtered solids with methylene chloride. Extract the aqueous base mixture with three 150 ml portions of methylene chloride. Combine all methylene chloride extracts and wash them with 75 ml of water followed by 75 ml of saturated sodium chloride solution. Dry the methylene chloride solution over anhydrous sodium sulfate. Remove the drying agent by filtration and strip the solvent in vacuo to provide the title compound as the free base.

Workup

  1. temperaturea gentle reflux of the solvent
  2. temperatureis maintained
  3. additionAfter the addition
  4. customis thoroughly reacted
  5. temperatureCool the reaction mixture to 40°-45° C.
  6. additionWhen the addition
  7. temperatureis complete reflux the mixture for 1 hour
  8. customthe progress of the reaction by thin-layer chromatography on silica gel (acetonitrile: ammonium hydroxide, 95:5)
  9. temperatureAt the completion of the reaction cool the mixture to 0°-5° C. in an ice/water bath
  10. customQuench the reaction mixture
  11. additionby the slow addition of 20 ml of 10% hydrochloric acid solution
  12. customRemove the tetrahydrofuran in vacuo
  13. additionAdd 100 ml of water to the residue
  14. additionthen add sufficient 10% sodium hydroxide
  15. temperaturewith cooling
  16. customRemove any magnesium hydroxide which
  17. custommay have precipitated by filtration
  18. washwash the filtered solids with methylene chloride
  19. extractionExtract the aqueous base mixture with three 150 ml portions of methylene chloride
  20. washwash them with 75 ml of water
  21. dry with materialDry the methylene chloride solution over anhydrous sodium sulfate
  22. customRemove the drying agent
  23. filtrationby filtration and strip the solvent in vacuo

Sources & evidence

ORD record
ord-a02883aad14348be9a09cb5482b00952
Source dataset
uspto-grants-1986_07
Patent number
US04599344

Reaction notes

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