3-Quinuclidinol, (-)- → HCID 58348365, compound

HRID 2192324Notes

Reaction equation

HRID 2192324 reaction equation
[CH3:1][O:2][C:3]([C:5]1([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].[N:19]12[CH2:26]C[CH:22]([CH2:23][CH2:24]1)[C@@H:21](O)[CH2:20]2>C1(C)C=CC=CC=1>[N:19]12[CH2:24][CH2:23][CH:22]([CH2:21][CH2:20]1)[C@@H:1]([O:2][C:3]([C:5]1([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1)=[O:4])[CH2:26]2

Participants

4

Reactant 2

HCID 914043-Quinuclidinol, (-)-HCID 58348374HCID 58348374, compound

Product 1

HCID 58348365HCID 58348365, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1-(3-Fluoro-phenyl)-cycloheptanecarboxylic acid methyl ester (Example 12c) (0.280 g) was dissolved in toluene (100 mL) and (R)-quinuclidin-3-ol (0.320 g) was added. Toluene (10 mL) was distilled off in a Dean and Stark apparatus and after cooling sodium hydride (10 mg) was added. The reaction was refluxed in a Dean and Stark apparatus for 4 hours after which time an extra amount of sodium hydride (10 mg) was added and the reaction was heated to reflux for a further 4 hours. After allowing to cool to room temperature, the toluene was washed with water, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with ethyl acetate/isohexane/triethylamine (50/50/ 1) then ethyl acetate/triethylamine (99/1) to afford the sub-titled compound (0.200 g

Workup

  1. distillationToluene (10 mL) was distilled off in a Dean and Stark apparatus
  2. temperatureafter cooling sodium hydride (10 mg)
  3. additionwas added
  4. temperatureThe reaction was refluxed in a Dean and Stark apparatus for 4 hours after which time an extra amount of sodium hydride (10 mg)
  5. additionwas added
  6. temperaturethe reaction was heated
  7. temperatureto reflux for a further 4 hours
  8. washthe toluene was washed with water
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customThe residue was purified by column chromatography
  12. washeluting with ethyl acetate/isohexane/triethylamine (50/50/ 1)

Sources & evidence

ORD record
ord-31695b95d0a04f78a0f9d19f34fff3d3
Source dataset
uspto-grants-2012_12
Patent number
US08329729B2

Reaction notes

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