3-Quinuclidinone → HCID 10206384, compound

HRID 2216383Notes

Reaction equation

HRID 2216383 reaction equation
[CH2:1]([C:8]1[C:13]([C:14]#[C:15][C:16]23[CH2:22][CH:19]([CH2:20]C2)CC3O)=[CH:12][CH:11]=[C:10]([N:24]2[CH2:28][C@@H:27]([O:29][CH3:30])[C@H:26]([OH:31])[CH2:25]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1CCCCC1.CCCCCC.C([Li])(CC)C.[N:49]12[CH2:56][CH2:55][CH:52]([CH2:53][CH2:54]1)[C:51](=[O:57])[CH2:50]2>O1CCCC1>[CH2:1]([C:8]1[C:13]([C:14]2[CH:20]=[CH:19][C:22]([C:51]3([OH:57])[CH:52]4[CH2:55][CH2:56][N:49]([CH2:54][CH2:53]4)[CH2:50]3)=[CH:16][CH:15]=2)=[CH:12][CH:11]=[C:10]([N:24]2[CH2:28][C@@H:27]([O:29][CH3:30])[C@H:26]([OH:31])[CH2:25]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 195073-QuinuclidinoneHCID 22494920Cyclohexane hexaneHCID 69362456HCID 69362456, compoundHCID 178418400CID 53628100

Product 1

HCID 10206384HCID 10206384, compoundYield 18.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-90 °C

Procedure

To a mixture of 280 mg of 2-(4-bromophenyl)-6-methyl-1,3,6,2-dioxyazaborocane (Production Example 14) and 10 ml of tetrahydrofuran was added dropwise 2 ml of a 1 M cyclohexane-hexane solution of sec-butyllithium under nitrogen atmosphere while cooling in a liquid nitrogen-tetrahydrofuran bath at −90° C., followed by stirring as it was for 40 minutes. Then, a solution of 130 mg of 3-quinuclidinone in 1 ml of tetrahydrofuran was added to the mixture, the liquid nitrogen-tetrahydrofuran bath was removed and the mixture was stirred at room temperature for 30 minutes. 1 ml of an aqueous ammonium chloride solution was added to the reaction mixture, followed by evaporating. To the residue were added 5 ml of methanol, 2 ml of a 5 Maqueous solution of potassium carbonate, 220 mg of 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridine hydrochloride and 5 ml of diethoxymethane, followed by heating under stirring under nitrogen atmosphere in an oil bath at 60° C. for 3 hours. The reaction mixture was extracted with ethyl acetate-water, and the organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and then evaporated. The residue was subjected to column chromatography using NH-silica gel with 50% ethyl acetate-hexane and 0–5% methanol-ethyl acetate, to give 60 mg of the title compound.

Workup

  1. customthe liquid nitrogen-tetrahydrofuran bath was removed
  2. stirringthe mixture was stirred at room temperature for 30 minutes
  3. addition1 ml of an aqueous ammonium chloride solution was added to the reaction mixture
  4. customby evaporating
  5. additionTo the residue were added 5 ml of methanol, 2 ml of a 5 Maqueous solution of potassium carbonate, 220 mg of 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridine hydrochloride and 5 ml of diethoxymethane
  6. temperatureby heating
  7. stirringunder stirring under nitrogen atmosphere in an oil bath at 60° C. for 3 hours
  8. extractionThe reaction mixture was extracted with ethyl acetate-water
  9. washthe organic layer was washed with water and brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customevaporated

Sources & evidence

ORD record
ord-a753d4811dd947fe96ddfc5dee5e166f
Source dataset
uspto-grants-2006_09
Patent number
US07112593B2

Reaction notes

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