Sodium hydride → HCID 86688913, compound

HRID 404654Notes

Reaction equation

HRID 404654 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([OH:9])[CH2:2]2.[H-].[Na+].[CH3:12][CH:13]1[CH2:18][CH:17]([CH3:19])[CH2:16][N:15]([CH:20]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:21](OCC)=[O:22])[CH2:14]1>C1(C)C=CC=CC=1>[CH3:12][CH:13]1[CH2:18][CH:17]([CH3:19])[CH2:16][N:15]([CH:20]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:21]([O:9][C@@H:3]2[CH:4]3[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]3)[CH2:2]2)=[O:22])[CH2:14]1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 914043-Quinuclidinol, (-)-HCID 86688912HCID 86688912, compound

Product 1

HCID 86688913HCID 86688913, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(R)-quinuclidin-3-ol (175 mg, 1.38 mmol) and NaH (60% dispersion in mineral oil, 52.3 mg, 1.31 mmol) were suspended in dry toluene (9 ml) under nitrogen atmosphere and stirred at room temperature for 20 minutes. Ethyl 2-(3,5-dimethylpiperidin-1-yl)-2-phenylacetate (200 mg, 0.73 mmol) was added and the resulting mixture was stirred at 100° C. for 24 hours. NaH (60% dispersion in mineral oil, 8.72 mg, 0.36 mmol) was added again and the mixture was refluxed for others 24 hours. The reaction was cooled and partitioned between water and ethyl ether. The organic layer was collected and dried over Na2SO4, filtered and evaporated. The crude compound was purified by flash chromatography (DCM/MeOH=9/1) to obtain (R)-quinuclidin-3-yl 2-(3,5-dimethylpiperidin-1-yl)-2-phenylacetate (125 mg, 48.3% yield) as a colourless oil.

Workup

  1. stirringthe resulting mixture was stirred at 100° C. for 24 hours
  2. temperaturethe mixture was refluxed for others 24 hours
  3. temperatureThe reaction was cooled
  4. custompartitioned between water and ethyl ether
  5. customThe organic layer was collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude compound was purified by flash chromatography (DCM/MeOH=9/1)

Sources & evidence

ORD record
ord-fa757006d61643a695b4e84475a1cdf0
Source dataset
uspto-grants-2014_06
Patent number
US08748613B2

Reaction notes

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