Methanol → 3-Ethynyl-1-azabicyclo[2.2.2]octan-3-ol

HRID 861423Notes

Reaction equation

HRID 861423 reaction equation
[C:1]([C:3]1([O:11]C(=O)CCC)[CH:8]2[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]2)[CH2:4]1)#[CH:2].CO.[OH-].[Na+]>O.S([O-])([O-])(=O)=O.[NH4+].[NH4+]>[C:1]([C:3]1([OH:11])[CH:8]2[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]2)[CH2:4]1)#[CH:2]

Participants

6

Reactant 3

HCID 887MethanolHCID 14798Sodium Hydroxide2×HCID 54501015HCID 54501015, compound

Product 1

HCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-olYield 18.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6097028Ammonium SulfateSolvent

Procedure

A solution of (±)-3-ethynyl-3-butyryloxyquinuclidine (4.42 g) in deionised water (700 ml) containing methanol (35 ml) was adjusted to pH 7.0 using an 0.1M aqueous sodium hydroxide solution (dispensed by a pH autotitrater). A suspension of pig liver eaterase (8.0 ml, 9200 units, in 3.2M aqueous ammonium sulphate solution at pH8; Sigma Chemical Company Ltd) was added to the reaction mixture and the mixture was stirred at ambient temperature whilst maintaining the pH at 7.0 using 0.1M aqueous sodium hydroxide solution (dispensed by a pH autotitrater). After 5.5 hours, 7.3 ml of the sodium hydroxide solution had been consumed, indicating that the hydrolysis was 35% complete. The pH of the reaction mixture was adjusted to 2.5 using 2M aqueous hydrochloric acid and the mixture was stirred for 10 minutes. 2M aqueous sodium hydroxide solution was then added to the mixture to give a pH of 7.05 and the mixture extracted with diethyl ether (3×200 ml, followed by 12×150 ml). The aqueous phase was separated, and freeze dried over a period of 48 hours to give a solid which was dissolved in deionised water (30 ml). The solution was filtered and the filtrate was basified to pH9 using 10.8M sodium hydroxide solution to give a solid. The solid was collected by filtration to give (+)-3-ethynyl-3-hydroxyquinuclidine, (554 mg) m.p. 204°-207° C., [α]20D =54.5° (C=0.99, methanol).

Workup

  1. additionwas added to the reaction mixture
  2. custom7.3 ml of the sodium hydroxide solution had been consumed
  3. stirringthe mixture was stirred for 10 minutes
  4. addition2M aqueous sodium hydroxide solution was then added to the mixture
  5. customto give a pH of 7.05
  6. extractionthe mixture extracted with diethyl ether (3×200 ml, followed by 12×150 ml)
  7. customThe aqueous phase was separated
  8. customfreeze dried over a period of 48 hours
  9. customto give a solid which
  10. filtrationThe solution was filtered
  11. customto give a solid
  12. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-20987203ff004432aebbfc2361ca824d
Source dataset
uspto-grants-1998_02
Patent number
US05714496

Reaction notes

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